CFGparadigms - User contributions [en]

F17G/GafD

2010-07-29T08:54:22Z

Julie Bouckaert: /* Biosynthesis of ligands */

The F17-G (GafD) adhesin at the tip of flexible F17 fimbriae of enterotoxigenic ''Escherichia coli'' mediates binding to N-acetyl-β-D-glucosamine-presenting receptors on the microvilli of the intestinal epithelium of ruminants, leading to diarrhea or septicaemia. F17-G belong to two-domain adhesins (TDA)s consisting of a pilin domain and a lectin domain, both having an Ig-fold joined via a short interdomain linker
<ref name=" Buts, L2003">
Buts, L., Bouckaert, J., De Gents, E., Loris, R., Oscarson, S., Lahmann, M., Messens, J., Brosens, E., Wyns, L. & De Greve, H. (2003). The fimbrial adhesin F17-G of enterotoxigenic Escherichia coli has an immunoglobulin-like lectin domain that binds N-acetylglucosamine. Mol. Microb. 49, 705-715.</ref><ref>Merckel, M. C., Tanskanen, J., Edelman, S., Westerlund-Wilkström, B., Korhonen, T. K. & Goldman, A. (2003). The structural basis of receptor-binding by Escherichia coli associaed with diarrhea and septicemia. J. Mol. Biol. 331, 897-905.</ref>. Related adhesins have been characterized in enteropathogenic ''E. coli'' ( FedF on F18 fimbriae<ref>Coddens, A., Diswall, M., Angstrom, J., Breimer, M. E., Goddeeris, B., Cox, E. & Teneberg, S. (2009). Recognition of blood group ABH type 1 determinants by the FedF adhesin of F18-fimbriated Escherichia coli. J Biol Chem 284, 9713-26.</ref> and CfaE on CFA/I pili<ref>Poole, S. T., McVeigh, A. L., Anantha, R. P., Lee, L. H., Akay, Y. M., Pontzer, E. A., Scott, D. A., Bullitt, E. & Savarino, S. J. (2007). Donor strand complementation governs intersubunit interaction of fimbriae of the alternate chaperone pathway. Mol Microbiol 63, 1372-84.</ref>) ) and uropathogenic ones (FimH on type 1 fimbriae<ref>Bouckaert, J., Berglund, J., Schembri, M., De Gents, E., Cools, L., Wuhrer, M., Hung, C.-S., Pinkner, J., Slättegard, R., Savialov, A., Choudhury, D., Langermann, S., Hultgren, S. J., Wyns, L., Klemm, P., Oscarson, S., Knight, S. D. & De Greve, H. (2005). Receptor binding studies disclose a novel class of high-affinity inhibitors of the Escherichia coli FimH adhesin. Mol. Microb. 55, 441-455.</ref> and PapG on P-pili<ref>Dodson, K. W., Pinkner, J. S., Rose, T., Magnusson, G., Hultgren, S. J. & Waksman, G. (2001). Structural basis of the interaction of the pyelonephritic E. coli adhesin to ist human kideny receptor. Cell 105, 733-743.</ref>). Fimbrial adhesins from other organisms, such as CupB6 from ''Pseudomonas aeruginosa'' are also investigated. All share the immunoglobulin-like fold of the two structural components, despite lack of any sequence identity and diversity in carbohydrate specificity and binding site, and the corresponding pili are assembled by the chaperone-usher pathway<ref>De Greve, H., Wyns, L. & Bouckaert, J. (2007). Combining sites of bacterial fimbriae. Curr Opin Struct Biol 17, 506-12.</ref><ref>Sauer, F. G., Barnhart, M., Choudhury, D., Knight, S. D., Waksman, G. & Hultgren, S. J. (2000). Chaperone-assisted pilus assembly and bacterial attachment. Curr Opin Struct Biol 10, 548-56.</ref>. The paradigm is unique among TAD for his specificity toward GlcNAc. The binding site is located laterally and not at the tip of the pili, therefore the long and flexible F17 fimbriae could intrude between the microvilli of the epithelium, with the binding site of the lectin domain interacting laterally with GlcNAc-containing receptors. Five naturally occurring variants, differing in 1-18 amino acids of the adhesion domain have been identified<ref>De Kerpel, M., Van Molle, I., Brys, L., Wyns, L., De Greve, H. & Bouckaert, J. (2006). N-terminal truncation enables crystallization of the receptor-binding domain of the FedF bacterial adhesin. Acta Crystallogr Sect F Struct Biol Cryst Commun 62, 1278-82.</ref>.

== CFG Participating Investigators contributing to the understanding of this paradigm ==
This is an emerging field of investigation and contributions arose from a small number of CFG Participating Investigators (PIs). These include: Esther Bullit, Eric Cox, Anne Imberty, Remy Loris, James Nataro

== Progress toward understanding this GBP paradigm ==

=== Carbohydrate ligands ===

The F17G adhesin is most specific for the disaccharide GlcNAcb1,3Gal that can be recognised as a terminal or internal sequence in bovine glycophorin <ref>Mouricout, M., Milhavet, M., Durié, C., Grange, P. Characterization of glycoprotein glycan receptors for Escherichia coli F17 fimbrial lectin, Microb. Pathog. (1995) 18, 297-306</ref>:
 
[[File:carbSynthe_0691_D000.jpg]]
 
The branched form gives a closely similar fluorescent signal:
 
[[File:carbSynthe_0897_D000.jpg]]
 
The presence of the b1,3 linkage of N-acetyl glucosamine to galactose enhances the affinity for F17G at least 2-fold, compared to the monosaccharide N-acetyl glucosamine, as validated using surface plasmon resonance measurements. Second best binders are the b1,4 and b1,6 galactose linked disaccharides, whereas chitobiose, that is also a characterized inhibitor of F17G-mediated bacterial adhesion, is clearly lagging behind. F17G can thus be ranked under glycan binding proteins that display high selectivity.

=== Cellular expression of GBP and ligands ===

F17G adhesins are expressed on enterotoxigenic E. coli infecting neonatal lambs, calves, and goat kids.
The F17G ligand GlcNAcb1,3Gal occurs universally but mostly internally in the sequence of poly-lactosaminyl glycans and blood group antigens.
These glycan structures are widely expressed on mamalian cell surfaces .

=== Biosynthesis of ligands ===
 
F17-fimbriated E. coli predominantly colonize neonatal animals, but also are a major causal agent (55%) of mastitis in bovines <ref>Lipman, L.J.A., de Nijs A., Gaastra W.. Isolation and identification of fimbriae and toxin production by Escherichia coli strains from cows with clinical mastitis, Vet. Microbiology 47 (1995) p. 1-7 </ref>. Congruent with the glycans recognized by F17G on the printed array versions 2.1 and 4.1, the N-acetyl glucosamine residue of GlcNAcb1,3Gal may be unsubstituted at the early life stage of calves, that are at the same time protected from bacterial infections by glycans secreted in the cow's milk.

=== Structure ===

The F17G adhesin is a two-domain adhesin (TDA) located at the F17 fimbrial tip. The determination of the crystal structure of the F17G lectin domain led to the discovery of the variable immunoglobulin-like structure
as a paradigm for bacterial fimbrial TDAs <ref name=" Buts, L2003">
</ref>. F17G has a shallow groove for carbohydrate recognition on its flank.

 
[[File:F17G_Igfold.jpg]]
 

=== Biological roles of GBP-ligand interaction ===

The F17G fimbrial lectin enhances intestinal colonization in the early life of ruminants. The long and flexible F17 fimbriae can penetrate deep between intestinal microvilli, where the fimbrial tip adhesin finds its glycan receptors. The subsequent secretion of heat stable and heat lable toxins can lead to severe diarhea.

== CFG resources used in investigations ==
The best examples of CFG contributions to this paradigm are described below, with links to specific data sets. For a complete list of CFG data and resources relating to this paradigm, see the CFG database search results for [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=fimbriae&maxresults=20 fimbriae] and [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=pili&maxresults=20 pili].

=== Glycan profiling ===

 
=== Glycogene microarray ===

 
=== Knockout mouse lines ===

 
=== Glycan array ===
F17G adhesins have been screened for their glycan specificity (click [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_PA_v2_177_11182005 here]). To see all glycan array results for F17G adhesin, click [http://www.functionalglycomics.org/glycomics/search/jsp/result.jsp?query=F17G&cat=coreh here].

== Related GBPs ==
FedF, CfaE, FimH, PapG, CupB6

The specificity of some of the other fimbrial tip adhesins was determined by CFG glycan array analysis ([http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_2358 ''P. gingivalis'' fimbriae], [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_PA_v2_178_11182005 ''E. coli'' FedF adhesin], [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_1106 ''E. coli'' CfaE adhesin from CFA/I pili])

== References ==
<references/>

== Acknowledgements ==
The CFG is grateful to the following PIs for their contributions to this wiki page: Alisdair Boraston, Julie Bouckaert, Anne Imberty

F17G/GafD

2010-07-29T08:53:49Z

Julie Bouckaert: /* Biosynthesis of ligands */

The F17-G (GafD) adhesin at the tip of flexible F17 fimbriae of enterotoxigenic ''Escherichia coli'' mediates binding to N-acetyl-β-D-glucosamine-presenting receptors on the microvilli of the intestinal epithelium of ruminants, leading to diarrhea or septicaemia. F17-G belong to two-domain adhesins (TDA)s consisting of a pilin domain and a lectin domain, both having an Ig-fold joined via a short interdomain linker
<ref name=" Buts, L2003">
Buts, L., Bouckaert, J., De Gents, E., Loris, R., Oscarson, S., Lahmann, M., Messens, J., Brosens, E., Wyns, L. & De Greve, H. (2003). The fimbrial adhesin F17-G of enterotoxigenic Escherichia coli has an immunoglobulin-like lectin domain that binds N-acetylglucosamine. Mol. Microb. 49, 705-715.</ref><ref>Merckel, M. C., Tanskanen, J., Edelman, S., Westerlund-Wilkström, B., Korhonen, T. K. & Goldman, A. (2003). The structural basis of receptor-binding by Escherichia coli associaed with diarrhea and septicemia. J. Mol. Biol. 331, 897-905.</ref>. Related adhesins have been characterized in enteropathogenic ''E. coli'' ( FedF on F18 fimbriae<ref>Coddens, A., Diswall, M., Angstrom, J., Breimer, M. E., Goddeeris, B., Cox, E. & Teneberg, S. (2009). Recognition of blood group ABH type 1 determinants by the FedF adhesin of F18-fimbriated Escherichia coli. J Biol Chem 284, 9713-26.</ref> and CfaE on CFA/I pili<ref>Poole, S. T., McVeigh, A. L., Anantha, R. P., Lee, L. H., Akay, Y. M., Pontzer, E. A., Scott, D. A., Bullitt, E. & Savarino, S. J. (2007). Donor strand complementation governs intersubunit interaction of fimbriae of the alternate chaperone pathway. Mol Microbiol 63, 1372-84.</ref>) ) and uropathogenic ones (FimH on type 1 fimbriae<ref>Bouckaert, J., Berglund, J., Schembri, M., De Gents, E., Cools, L., Wuhrer, M., Hung, C.-S., Pinkner, J., Slättegard, R., Savialov, A., Choudhury, D., Langermann, S., Hultgren, S. J., Wyns, L., Klemm, P., Oscarson, S., Knight, S. D. & De Greve, H. (2005). Receptor binding studies disclose a novel class of high-affinity inhibitors of the Escherichia coli FimH adhesin. Mol. Microb. 55, 441-455.</ref> and PapG on P-pili<ref>Dodson, K. W., Pinkner, J. S., Rose, T., Magnusson, G., Hultgren, S. J. & Waksman, G. (2001). Structural basis of the interaction of the pyelonephritic E. coli adhesin to ist human kideny receptor. Cell 105, 733-743.</ref>). Fimbrial adhesins from other organisms, such as CupB6 from ''Pseudomonas aeruginosa'' are also investigated. All share the immunoglobulin-like fold of the two structural components, despite lack of any sequence identity and diversity in carbohydrate specificity and binding site, and the corresponding pili are assembled by the chaperone-usher pathway<ref>De Greve, H., Wyns, L. & Bouckaert, J. (2007). Combining sites of bacterial fimbriae. Curr Opin Struct Biol 17, 506-12.</ref><ref>Sauer, F. G., Barnhart, M., Choudhury, D., Knight, S. D., Waksman, G. & Hultgren, S. J. (2000). Chaperone-assisted pilus assembly and bacterial attachment. Curr Opin Struct Biol 10, 548-56.</ref>. The paradigm is unique among TAD for his specificity toward GlcNAc. The binding site is located laterally and not at the tip of the pili, therefore the long and flexible F17 fimbriae could intrude between the microvilli of the epithelium, with the binding site of the lectin domain interacting laterally with GlcNAc-containing receptors. Five naturally occurring variants, differing in 1-18 amino acids of the adhesion domain have been identified<ref>De Kerpel, M., Van Molle, I., Brys, L., Wyns, L., De Greve, H. & Bouckaert, J. (2006). N-terminal truncation enables crystallization of the receptor-binding domain of the FedF bacterial adhesin. Acta Crystallogr Sect F Struct Biol Cryst Commun 62, 1278-82.</ref>.

== CFG Participating Investigators contributing to the understanding of this paradigm ==
This is an emerging field of investigation and contributions arose from a small number of CFG Participating Investigators (PIs). These include: Esther Bullit, Eric Cox, Anne Imberty, Remy Loris, James Nataro

== Progress toward understanding this GBP paradigm ==

=== Carbohydrate ligands ===

The F17G adhesin is most specific for the disaccharide GlcNAcb1,3Gal that can be recognised as a terminal or internal sequence in bovine glycophorin <ref>Mouricout, M., Milhavet, M., Durié, C., Grange, P. Characterization of glycoprotein glycan receptors for Escherichia coli F17 fimbrial lectin, Microb. Pathog. (1995) 18, 297-306</ref>:
 
[[File:carbSynthe_0691_D000.jpg]]
 
The branched form gives a closely similar fluorescent signal:
 
[[File:carbSynthe_0897_D000.jpg]]
 
The presence of the b1,3 linkage of N-acetyl glucosamine to galactose enhances the affinity for F17G at least 2-fold, compared to the monosaccharide N-acetyl glucosamine, as validated using surface plasmon resonance measurements. Second best binders are the b1,4 and b1,6 galactose linked disaccharides, whereas chitobiose, that is also a characterized inhibitor of F17G-mediated bacterial adhesion, is clearly lagging behind. F17G can thus be ranked under glycan binding proteins that display high selectivity.

=== Cellular expression of GBP and ligands ===

F17G adhesins are expressed on enterotoxigenic E. coli infecting neonatal lambs, calves, and goat kids.
The F17G ligand GlcNAcb1,3Gal occurs universally but mostly internally in the sequence of poly-lactosaminyl glycans and blood group antigens.
These glycan structures are widely expressed on mamalian cell surfaces .

=== Biosynthesis of ligands ===
 
F17-fimbriated E. coli predominantly colonize neonatal animals, but also are a major causal agent (55%) of mastitis in bovines <ref>Lipman, L.J.A., de Nijs A., Gaastra W.. Isolation and identification of fimbriae and toxin production by Escherichia coli strains from cows with clinical mastitis, Vet. Microbiology 47 (1995) p. 1-7 </ref>. Congruent with the glycans recognized by F17G on the printed array versions 2.1 and 4.1, the N-acetyl glucosamine residue of GlcNAcb1,3Gal may be unsubstituted at the early life stage of calves, that are at the same time protected from bacterial infection by glycans secreted in the cow's milk.

=== Structure ===

The F17G adhesin is a two-domain adhesin (TDA) located at the F17 fimbrial tip. The determination of the crystal structure of the F17G lectin domain led to the discovery of the variable immunoglobulin-like structure
as a paradigm for bacterial fimbrial TDAs <ref name=" Buts, L2003">
</ref>. F17G has a shallow groove for carbohydrate recognition on its flank.

 
[[File:F17G_Igfold.jpg]]
 

=== Biological roles of GBP-ligand interaction ===

The F17G fimbrial lectin enhances intestinal colonization in the early life of ruminants. The long and flexible F17 fimbriae can penetrate deep between intestinal microvilli, where the fimbrial tip adhesin finds its glycan receptors. The subsequent secretion of heat stable and heat lable toxins can lead to severe diarhea.

== CFG resources used in investigations ==
The best examples of CFG contributions to this paradigm are described below, with links to specific data sets. For a complete list of CFG data and resources relating to this paradigm, see the CFG database search results for [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=fimbriae&maxresults=20 fimbriae] and [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=pili&maxresults=20 pili].

=== Glycan profiling ===

 
=== Glycogene microarray ===

 
=== Knockout mouse lines ===

 
=== Glycan array ===
F17G adhesins have been screened for their glycan specificity (click [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_PA_v2_177_11182005 here]). To see all glycan array results for F17G adhesin, click [http://www.functionalglycomics.org/glycomics/search/jsp/result.jsp?query=F17G&cat=coreh here].

== Related GBPs ==
FedF, CfaE, FimH, PapG, CupB6

The specificity of some of the other fimbrial tip adhesins was determined by CFG glycan array analysis ([http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_2358 ''P. gingivalis'' fimbriae], [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_PA_v2_178_11182005 ''E. coli'' FedF adhesin], [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_1106 ''E. coli'' CfaE adhesin from CFA/I pili])

== References ==
<references/>

== Acknowledgements ==
The CFG is grateful to the following PIs for their contributions to this wiki page: Alisdair Boraston, Julie Bouckaert, Anne Imberty

F17G/GafD

2010-07-29T08:39:47Z

Julie Bouckaert: /* Cellular expression of GBP and ligands */

The F17-G (GafD) adhesin at the tip of flexible F17 fimbriae of enterotoxigenic ''Escherichia coli'' mediates binding to N-acetyl-β-D-glucosamine-presenting receptors on the microvilli of the intestinal epithelium of ruminants, leading to diarrhea or septicaemia. F17-G belong to two-domain adhesins (TDA)s consisting of a pilin domain and a lectin domain, both having an Ig-fold joined via a short interdomain linker
<ref name=" Buts, L2003">
Buts, L., Bouckaert, J., De Gents, E., Loris, R., Oscarson, S., Lahmann, M., Messens, J., Brosens, E., Wyns, L. & De Greve, H. (2003). The fimbrial adhesin F17-G of enterotoxigenic Escherichia coli has an immunoglobulin-like lectin domain that binds N-acetylglucosamine. Mol. Microb. 49, 705-715.</ref><ref>Merckel, M. C., Tanskanen, J., Edelman, S., Westerlund-Wilkström, B., Korhonen, T. K. & Goldman, A. (2003). The structural basis of receptor-binding by Escherichia coli associaed with diarrhea and septicemia. J. Mol. Biol. 331, 897-905.</ref>. Related adhesins have been characterized in enteropathogenic ''E. coli'' ( FedF on F18 fimbriae<ref>Coddens, A., Diswall, M., Angstrom, J., Breimer, M. E., Goddeeris, B., Cox, E. & Teneberg, S. (2009). Recognition of blood group ABH type 1 determinants by the FedF adhesin of F18-fimbriated Escherichia coli. J Biol Chem 284, 9713-26.</ref> and CfaE on CFA/I pili<ref>Poole, S. T., McVeigh, A. L., Anantha, R. P., Lee, L. H., Akay, Y. M., Pontzer, E. A., Scott, D. A., Bullitt, E. & Savarino, S. J. (2007). Donor strand complementation governs intersubunit interaction of fimbriae of the alternate chaperone pathway. Mol Microbiol 63, 1372-84.</ref>) ) and uropathogenic ones (FimH on type 1 fimbriae<ref>Bouckaert, J., Berglund, J., Schembri, M., De Gents, E., Cools, L., Wuhrer, M., Hung, C.-S., Pinkner, J., Slättegard, R., Savialov, A., Choudhury, D., Langermann, S., Hultgren, S. J., Wyns, L., Klemm, P., Oscarson, S., Knight, S. D. & De Greve, H. (2005). Receptor binding studies disclose a novel class of high-affinity inhibitors of the Escherichia coli FimH adhesin. Mol. Microb. 55, 441-455.</ref> and PapG on P-pili<ref>Dodson, K. W., Pinkner, J. S., Rose, T., Magnusson, G., Hultgren, S. J. & Waksman, G. (2001). Structural basis of the interaction of the pyelonephritic E. coli adhesin to ist human kideny receptor. Cell 105, 733-743.</ref>). Fimbrial adhesins from other organisms, such as CupB6 from ''Pseudomonas aeruginosa'' are also investigated. All share the immunoglobulin-like fold of the two structural components, despite lack of any sequence identity and diversity in carbohydrate specificity and binding site, and the corresponding pili are assembled by the chaperone-usher pathway<ref>De Greve, H., Wyns, L. & Bouckaert, J. (2007). Combining sites of bacterial fimbriae. Curr Opin Struct Biol 17, 506-12.</ref><ref>Sauer, F. G., Barnhart, M., Choudhury, D., Knight, S. D., Waksman, G. & Hultgren, S. J. (2000). Chaperone-assisted pilus assembly and bacterial attachment. Curr Opin Struct Biol 10, 548-56.</ref>. The paradigm is unique among TAD for his specificity toward GlcNAc. The binding site is located laterally and not at the tip of the pili, therefore the long and flexible F17 fimbriae could intrude between the microvilli of the epithelium, with the binding site of the lectin domain interacting laterally with GlcNAc-containing receptors. Five naturally occurring variants, differing in 1-18 amino acids of the adhesion domain have been identified<ref>De Kerpel, M., Van Molle, I., Brys, L., Wyns, L., De Greve, H. & Bouckaert, J. (2006). N-terminal truncation enables crystallization of the receptor-binding domain of the FedF bacterial adhesin. Acta Crystallogr Sect F Struct Biol Cryst Commun 62, 1278-82.</ref>.

== CFG Participating Investigators contributing to the understanding of this paradigm ==
This is an emerging field of investigation and contributions arose from a small number of CFG Participating Investigators (PIs). These include: Esther Bullit, Eric Cox, Anne Imberty, Remy Loris, James Nataro

== Progress toward understanding this GBP paradigm ==

=== Carbohydrate ligands ===

The F17G adhesin is most specific for the disaccharide GlcNAcb1,3Gal that can be recognised as a terminal or internal sequence in bovine glycophorin <ref>Mouricout, M., Milhavet, M., Durié, C., Grange, P. Characterization of glycoprotein glycan receptors for Escherichia coli F17 fimbrial lectin, Microb. Pathog. (1995) 18, 297-306</ref>:
 
[[File:carbSynthe_0691_D000.jpg]]
 
The branched form gives a closely similar fluorescent signal:
 
[[File:carbSynthe_0897_D000.jpg]]
 
The presence of the b1,3 linkage of N-acetyl glucosamine to galactose enhances the affinity for F17G at least 2-fold, compared to the monosaccharide N-acetyl glucosamine, as validated using surface plasmon resonance measurements. Second best binders are the b1,4 and b1,6 galactose linked disaccharides, whereas chitobiose, that is also a characterized inhibitor of F17G-mediated bacterial adhesion, is clearly lagging behind. F17G can thus be ranked under glycan binding proteins that display high selectivity.

=== Cellular expression of GBP and ligands ===

F17G adhesins are expressed on enterotoxigenic E. coli infecting neonatal lambs, calves, and goat kids.
The F17G ligand GlcNAcb1,3Gal occurs universally but mostly internally in the sequence of poly-lactosaminyl glycans and blood group antigens.
These glycan structures are widely expressed on mamalian cell surfaces .

=== Biosynthesis of ligands ===
 
The F17G ligand GlcNAcb1,3Gal occurs universally but internally in polylactosaminyl glycans and in blood group antigens, both which are widely expressed on mamalian cell surfaces.
F17-fimbriated E. coli predominantly colonize neonatal animals but also cause mastitis in bovine mammae<ref>Lipman, L.J.A., de Nijs A., Gaastra W.. Isolation and identification of fimbriae and toxin production by Escherichia coli strains from cows with clinical mastitis, Vet. Microbiology 47 (1995) p. 1-7 </ref> producing the milk that protects the calves against bacterial infections. The N-acetyl glucosamine residue of GlcNAcb1,3Gal may still be unsubstituted at this early life stage, congruent the glycans recognized by F17G on the glycan array.

=== Structure ===

The F17G adhesin is a two-domain adhesin (TDA) located at the F17 fimbrial tip. The determination of the crystal structure of the F17G lectin domain led to the discovery of the variable immunoglobulin-like structure
as a paradigm for bacterial fimbrial TDAs <ref name=" Buts, L2003">
</ref>. F17G has a shallow groove for carbohydrate recognition on its flank.

 
[[File:F17G_Igfold.jpg]]
 

=== Biological roles of GBP-ligand interaction ===

The F17G fimbrial lectin enhances intestinal colonization in the early life of ruminants. The long and flexible F17 fimbriae can penetrate deep between intestinal microvilli, where the fimbrial tip adhesin finds its glycan receptors. The subsequent secretion of heat stable and heat lable toxins can lead to severe diarhea.

== CFG resources used in investigations ==
The best examples of CFG contributions to this paradigm are described below, with links to specific data sets. For a complete list of CFG data and resources relating to this paradigm, see the CFG database search results for [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=fimbriae&maxresults=20 fimbriae] and [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=pili&maxresults=20 pili].

=== Glycan profiling ===

 
=== Glycogene microarray ===

 
=== Knockout mouse lines ===

 
=== Glycan array ===
F17G adhesins have been screened for their glycan specificity (click [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_PA_v2_177_11182005 here]). To see all glycan array results for F17G adhesin, click [http://www.functionalglycomics.org/glycomics/search/jsp/result.jsp?query=F17G&cat=coreh here].

== Related GBPs ==
FedF, CfaE, FimH, PapG, CupB6

The specificity of some of the other fimbrial tip adhesins was determined by CFG glycan array analysis ([http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_2358 ''P. gingivalis'' fimbriae], [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_PA_v2_178_11182005 ''E. coli'' FedF adhesin], [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_1106 ''E. coli'' CfaE adhesin from CFA/I pili])

== References ==
<references/>

== Acknowledgements ==
The CFG is grateful to the following PIs for their contributions to this wiki page: Alisdair Boraston, Julie Bouckaert, Anne Imberty

F17G/GafD

2010-07-29T08:35:10Z

Julie Bouckaert: /* Cellular expression of GBP and ligands */

The F17-G (GafD) adhesin at the tip of flexible F17 fimbriae of enterotoxigenic ''Escherichia coli'' mediates binding to N-acetyl-β-D-glucosamine-presenting receptors on the microvilli of the intestinal epithelium of ruminants, leading to diarrhea or septicaemia. F17-G belong to two-domain adhesins (TDA)s consisting of a pilin domain and a lectin domain, both having an Ig-fold joined via a short interdomain linker
<ref name=" Buts, L2003">
Buts, L., Bouckaert, J., De Gents, E., Loris, R., Oscarson, S., Lahmann, M., Messens, J., Brosens, E., Wyns, L. & De Greve, H. (2003). The fimbrial adhesin F17-G of enterotoxigenic Escherichia coli has an immunoglobulin-like lectin domain that binds N-acetylglucosamine. Mol. Microb. 49, 705-715.</ref><ref>Merckel, M. C., Tanskanen, J., Edelman, S., Westerlund-Wilkström, B., Korhonen, T. K. & Goldman, A. (2003). The structural basis of receptor-binding by Escherichia coli associaed with diarrhea and septicemia. J. Mol. Biol. 331, 897-905.</ref>. Related adhesins have been characterized in enteropathogenic ''E. coli'' ( FedF on F18 fimbriae<ref>Coddens, A., Diswall, M., Angstrom, J., Breimer, M. E., Goddeeris, B., Cox, E. & Teneberg, S. (2009). Recognition of blood group ABH type 1 determinants by the FedF adhesin of F18-fimbriated Escherichia coli. J Biol Chem 284, 9713-26.</ref> and CfaE on CFA/I pili<ref>Poole, S. T., McVeigh, A. L., Anantha, R. P., Lee, L. H., Akay, Y. M., Pontzer, E. A., Scott, D. A., Bullitt, E. & Savarino, S. J. (2007). Donor strand complementation governs intersubunit interaction of fimbriae of the alternate chaperone pathway. Mol Microbiol 63, 1372-84.</ref>) ) and uropathogenic ones (FimH on type 1 fimbriae<ref>Bouckaert, J., Berglund, J., Schembri, M., De Gents, E., Cools, L., Wuhrer, M., Hung, C.-S., Pinkner, J., Slättegard, R., Savialov, A., Choudhury, D., Langermann, S., Hultgren, S. J., Wyns, L., Klemm, P., Oscarson, S., Knight, S. D. & De Greve, H. (2005). Receptor binding studies disclose a novel class of high-affinity inhibitors of the Escherichia coli FimH adhesin. Mol. Microb. 55, 441-455.</ref> and PapG on P-pili<ref>Dodson, K. W., Pinkner, J. S., Rose, T., Magnusson, G., Hultgren, S. J. & Waksman, G. (2001). Structural basis of the interaction of the pyelonephritic E. coli adhesin to ist human kideny receptor. Cell 105, 733-743.</ref>). Fimbrial adhesins from other organisms, such as CupB6 from ''Pseudomonas aeruginosa'' are also investigated. All share the immunoglobulin-like fold of the two structural components, despite lack of any sequence identity and diversity in carbohydrate specificity and binding site, and the corresponding pili are assembled by the chaperone-usher pathway<ref>De Greve, H., Wyns, L. & Bouckaert, J. (2007). Combining sites of bacterial fimbriae. Curr Opin Struct Biol 17, 506-12.</ref><ref>Sauer, F. G., Barnhart, M., Choudhury, D., Knight, S. D., Waksman, G. & Hultgren, S. J. (2000). Chaperone-assisted pilus assembly and bacterial attachment. Curr Opin Struct Biol 10, 548-56.</ref>. The paradigm is unique among TAD for his specificity toward GlcNAc. The binding site is located laterally and not at the tip of the pili, therefore the long and flexible F17 fimbriae could intrude between the microvilli of the epithelium, with the binding site of the lectin domain interacting laterally with GlcNAc-containing receptors. Five naturally occurring variants, differing in 1-18 amino acids of the adhesion domain have been identified<ref>De Kerpel, M., Van Molle, I., Brys, L., Wyns, L., De Greve, H. & Bouckaert, J. (2006). N-terminal truncation enables crystallization of the receptor-binding domain of the FedF bacterial adhesin. Acta Crystallogr Sect F Struct Biol Cryst Commun 62, 1278-82.</ref>.

== CFG Participating Investigators contributing to the understanding of this paradigm ==
This is an emerging field of investigation and contributions arose from a small number of CFG Participating Investigators (PIs). These include: Esther Bullit, Eric Cox, Anne Imberty, Remy Loris, James Nataro

== Progress toward understanding this GBP paradigm ==

=== Carbohydrate ligands ===

The F17G adhesin is most specific for the disaccharide GlcNAcb1,3Gal that can be recognised as a terminal or internal sequence in bovine glycophorin <ref>Mouricout, M., Milhavet, M., Durié, C., Grange, P. Characterization of glycoprotein glycan receptors for Escherichia coli F17 fimbrial lectin, Microb. Pathog. (1995) 18, 297-306</ref>:
 
[[File:carbSynthe_0691_D000.jpg]]
 
The branched form gives a closely similar fluorescent signal:
 
[[File:carbSynthe_0897_D000.jpg]]
 
The presence of the b1,3 linkage of N-acetyl glucosamine to galactose enhances the affinity for F17G at least 2-fold, compared to the monosaccharide N-acetyl glucosamine, as validated using surface plasmon resonance measurements. Second best binders are the b1,4 and b1,6 galactose linked disaccharides, whereas chitobiose, that is also a characterized inhibitor of F17G-mediated bacterial adhesion, is clearly lagging behind. F17G can thus be ranked under glycan binding proteins that display high selectivity.

=== Cellular expression of GBP and ligands ===

F17G adhesins are expressed on enterotoxigenic E. coli infecting neonatal lambs, calves, and goat kids.

=== Biosynthesis of ligands ===
 
The F17G ligand GlcNAcb1,3Gal occurs universally but internally in polylactosaminyl glycans and in blood group antigens, both which are widely expressed on mamalian cell surfaces.
F17-fimbriated E. coli predominantly colonize neonatal animals but also cause mastitis in bovine mammae<ref>Lipman, L.J.A., de Nijs A., Gaastra W.. Isolation and identification of fimbriae and toxin production by Escherichia coli strains from cows with clinical mastitis, Vet. Microbiology 47 (1995) p. 1-7 </ref> producing the milk that protects the calves against bacterial infections. The N-acetyl glucosamine residue of GlcNAcb1,3Gal may still be unsubstituted at this early life stage, congruent the glycans recognized by F17G on the glycan array.

=== Structure ===

The F17G adhesin is a two-domain adhesin (TDA) located at the F17 fimbrial tip. The determination of the crystal structure of the F17G lectin domain led to the discovery of the variable immunoglobulin-like structure
as a paradigm for bacterial fimbrial TDAs <ref name=" Buts, L2003">
</ref>. F17G has a shallow groove for carbohydrate recognition on its flank.

 
[[File:F17G_Igfold.jpg]]
 

=== Biological roles of GBP-ligand interaction ===

The F17G fimbrial lectin enhances intestinal colonization in the early life of ruminants. The long and flexible F17 fimbriae can penetrate deep between intestinal microvilli, where the fimbrial tip adhesin finds its glycan receptors. The subsequent secretion of heat stable and heat lable toxins can lead to severe diarhea.

== CFG resources used in investigations ==
The best examples of CFG contributions to this paradigm are described below, with links to specific data sets. For a complete list of CFG data and resources relating to this paradigm, see the CFG database search results for [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=fimbriae&maxresults=20 fimbriae] and [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=pili&maxresults=20 pili].

=== Glycan profiling ===

 
=== Glycogene microarray ===

 
=== Knockout mouse lines ===

 
=== Glycan array ===
F17G adhesins have been screened for their glycan specificity (click [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_PA_v2_177_11182005 here]). To see all glycan array results for F17G adhesin, click [http://www.functionalglycomics.org/glycomics/search/jsp/result.jsp?query=F17G&cat=coreh here].

== Related GBPs ==
FedF, CfaE, FimH, PapG, CupB6

The specificity of some of the other fimbrial tip adhesins was determined by CFG glycan array analysis ([http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_2358 ''P. gingivalis'' fimbriae], [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_PA_v2_178_11182005 ''E. coli'' FedF adhesin], [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_1106 ''E. coli'' CfaE adhesin from CFA/I pili])

== References ==
<references/>

== Acknowledgements ==
The CFG is grateful to the following PIs for their contributions to this wiki page: Alisdair Boraston, Julie Bouckaert, Anne Imberty

F17G/GafD

2010-07-29T08:34:39Z

Julie Bouckaert: /* Carbohydrate ligands */

The F17-G (GafD) adhesin at the tip of flexible F17 fimbriae of enterotoxigenic ''Escherichia coli'' mediates binding to N-acetyl-β-D-glucosamine-presenting receptors on the microvilli of the intestinal epithelium of ruminants, leading to diarrhea or septicaemia. F17-G belong to two-domain adhesins (TDA)s consisting of a pilin domain and a lectin domain, both having an Ig-fold joined via a short interdomain linker
<ref name=" Buts, L2003">
Buts, L., Bouckaert, J., De Gents, E., Loris, R., Oscarson, S., Lahmann, M., Messens, J., Brosens, E., Wyns, L. & De Greve, H. (2003). The fimbrial adhesin F17-G of enterotoxigenic Escherichia coli has an immunoglobulin-like lectin domain that binds N-acetylglucosamine. Mol. Microb. 49, 705-715.</ref><ref>Merckel, M. C., Tanskanen, J., Edelman, S., Westerlund-Wilkström, B., Korhonen, T. K. & Goldman, A. (2003). The structural basis of receptor-binding by Escherichia coli associaed with diarrhea and septicemia. J. Mol. Biol. 331, 897-905.</ref>. Related adhesins have been characterized in enteropathogenic ''E. coli'' ( FedF on F18 fimbriae<ref>Coddens, A., Diswall, M., Angstrom, J., Breimer, M. E., Goddeeris, B., Cox, E. & Teneberg, S. (2009). Recognition of blood group ABH type 1 determinants by the FedF adhesin of F18-fimbriated Escherichia coli. J Biol Chem 284, 9713-26.</ref> and CfaE on CFA/I pili<ref>Poole, S. T., McVeigh, A. L., Anantha, R. P., Lee, L. H., Akay, Y. M., Pontzer, E. A., Scott, D. A., Bullitt, E. & Savarino, S. J. (2007). Donor strand complementation governs intersubunit interaction of fimbriae of the alternate chaperone pathway. Mol Microbiol 63, 1372-84.</ref>) ) and uropathogenic ones (FimH on type 1 fimbriae<ref>Bouckaert, J., Berglund, J., Schembri, M., De Gents, E., Cools, L., Wuhrer, M., Hung, C.-S., Pinkner, J., Slättegard, R., Savialov, A., Choudhury, D., Langermann, S., Hultgren, S. J., Wyns, L., Klemm, P., Oscarson, S., Knight, S. D. & De Greve, H. (2005). Receptor binding studies disclose a novel class of high-affinity inhibitors of the Escherichia coli FimH adhesin. Mol. Microb. 55, 441-455.</ref> and PapG on P-pili<ref>Dodson, K. W., Pinkner, J. S., Rose, T., Magnusson, G., Hultgren, S. J. & Waksman, G. (2001). Structural basis of the interaction of the pyelonephritic E. coli adhesin to ist human kideny receptor. Cell 105, 733-743.</ref>). Fimbrial adhesins from other organisms, such as CupB6 from ''Pseudomonas aeruginosa'' are also investigated. All share the immunoglobulin-like fold of the two structural components, despite lack of any sequence identity and diversity in carbohydrate specificity and binding site, and the corresponding pili are assembled by the chaperone-usher pathway<ref>De Greve, H., Wyns, L. & Bouckaert, J. (2007). Combining sites of bacterial fimbriae. Curr Opin Struct Biol 17, 506-12.</ref><ref>Sauer, F. G., Barnhart, M., Choudhury, D., Knight, S. D., Waksman, G. & Hultgren, S. J. (2000). Chaperone-assisted pilus assembly and bacterial attachment. Curr Opin Struct Biol 10, 548-56.</ref>. The paradigm is unique among TAD for his specificity toward GlcNAc. The binding site is located laterally and not at the tip of the pili, therefore the long and flexible F17 fimbriae could intrude between the microvilli of the epithelium, with the binding site of the lectin domain interacting laterally with GlcNAc-containing receptors. Five naturally occurring variants, differing in 1-18 amino acids of the adhesion domain have been identified<ref>De Kerpel, M., Van Molle, I., Brys, L., Wyns, L., De Greve, H. & Bouckaert, J. (2006). N-terminal truncation enables crystallization of the receptor-binding domain of the FedF bacterial adhesin. Acta Crystallogr Sect F Struct Biol Cryst Commun 62, 1278-82.</ref>.

== CFG Participating Investigators contributing to the understanding of this paradigm ==
This is an emerging field of investigation and contributions arose from a small number of CFG Participating Investigators (PIs). These include: Esther Bullit, Eric Cox, Anne Imberty, Remy Loris, James Nataro

== Progress toward understanding this GBP paradigm ==

=== Carbohydrate ligands ===

The F17G adhesin is most specific for the disaccharide GlcNAcb1,3Gal that can be recognised as a terminal or internal sequence in bovine glycophorin <ref>Mouricout, M., Milhavet, M., Durié, C., Grange, P. Characterization of glycoprotein glycan receptors for Escherichia coli F17 fimbrial lectin, Microb. Pathog. (1995) 18, 297-306</ref>:
 
[[File:carbSynthe_0691_D000.jpg]]
 
The branched form gives a closely similar fluorescent signal:
 
[[File:carbSynthe_0897_D000.jpg]]
 
The presence of the b1,3 linkage of N-acetyl glucosamine to galactose enhances the affinity for F17G at least 2-fold, compared to the monosaccharide N-acetyl glucosamine, as validated using surface plasmon resonance measurements. Second best binders are the b1,4 and b1,6 galactose linked disaccharides, whereas chitobiose, that is also a characterized inhibitor of F17G-mediated bacterial adhesion, is clearly lagging behind. F17G can thus be ranked under glycan binding proteins that display high selectivity.

=== Cellular expression of GBP and ligands ===

F17G adhesins are constitutively expressed on enterotoxigenic E. coli infecting neonatal lambs, calves, and goat kids.

=== Biosynthesis of ligands ===
 
The F17G ligand GlcNAcb1,3Gal occurs universally but internally in polylactosaminyl glycans and in blood group antigens, both which are widely expressed on mamalian cell surfaces.
F17-fimbriated E. coli predominantly colonize neonatal animals but also cause mastitis in bovine mammae<ref>Lipman, L.J.A., de Nijs A., Gaastra W.. Isolation and identification of fimbriae and toxin production by Escherichia coli strains from cows with clinical mastitis, Vet. Microbiology 47 (1995) p. 1-7 </ref> producing the milk that protects the calves against bacterial infections. The N-acetyl glucosamine residue of GlcNAcb1,3Gal may still be unsubstituted at this early life stage, congruent the glycans recognized by F17G on the glycan array.

=== Structure ===

The F17G adhesin is a two-domain adhesin (TDA) located at the F17 fimbrial tip. The determination of the crystal structure of the F17G lectin domain led to the discovery of the variable immunoglobulin-like structure
as a paradigm for bacterial fimbrial TDAs <ref name=" Buts, L2003">
</ref>. F17G has a shallow groove for carbohydrate recognition on its flank.

 
[[File:F17G_Igfold.jpg]]
 

=== Biological roles of GBP-ligand interaction ===

The F17G fimbrial lectin enhances intestinal colonization in the early life of ruminants. The long and flexible F17 fimbriae can penetrate deep between intestinal microvilli, where the fimbrial tip adhesin finds its glycan receptors. The subsequent secretion of heat stable and heat lable toxins can lead to severe diarhea.

== CFG resources used in investigations ==
The best examples of CFG contributions to this paradigm are described below, with links to specific data sets. For a complete list of CFG data and resources relating to this paradigm, see the CFG database search results for [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=fimbriae&maxresults=20 fimbriae] and [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=pili&maxresults=20 pili].

=== Glycan profiling ===

 
=== Glycogene microarray ===

 
=== Knockout mouse lines ===

 
=== Glycan array ===
F17G adhesins have been screened for their glycan specificity (click [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_PA_v2_177_11182005 here]). To see all glycan array results for F17G adhesin, click [http://www.functionalglycomics.org/glycomics/search/jsp/result.jsp?query=F17G&cat=coreh here].

== Related GBPs ==
FedF, CfaE, FimH, PapG, CupB6

The specificity of some of the other fimbrial tip adhesins was determined by CFG glycan array analysis ([http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_2358 ''P. gingivalis'' fimbriae], [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_PA_v2_178_11182005 ''E. coli'' FedF adhesin], [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_1106 ''E. coli'' CfaE adhesin from CFA/I pili])

== References ==
<references/>

== Acknowledgements ==
The CFG is grateful to the following PIs for their contributions to this wiki page: Alisdair Boraston, Julie Bouckaert, Anne Imberty

F17G/GafD

2010-07-29T08:34:03Z

Julie Bouckaert: /* Carbohydrate ligands */

The F17-G (GafD) adhesin at the tip of flexible F17 fimbriae of enterotoxigenic ''Escherichia coli'' mediates binding to N-acetyl-β-D-glucosamine-presenting receptors on the microvilli of the intestinal epithelium of ruminants, leading to diarrhea or septicaemia. F17-G belong to two-domain adhesins (TDA)s consisting of a pilin domain and a lectin domain, both having an Ig-fold joined via a short interdomain linker
<ref name=" Buts, L2003">
Buts, L., Bouckaert, J., De Gents, E., Loris, R., Oscarson, S., Lahmann, M., Messens, J., Brosens, E., Wyns, L. & De Greve, H. (2003). The fimbrial adhesin F17-G of enterotoxigenic Escherichia coli has an immunoglobulin-like lectin domain that binds N-acetylglucosamine. Mol. Microb. 49, 705-715.</ref><ref>Merckel, M. C., Tanskanen, J., Edelman, S., Westerlund-Wilkström, B., Korhonen, T. K. & Goldman, A. (2003). The structural basis of receptor-binding by Escherichia coli associaed with diarrhea and septicemia. J. Mol. Biol. 331, 897-905.</ref>. Related adhesins have been characterized in enteropathogenic ''E. coli'' ( FedF on F18 fimbriae<ref>Coddens, A., Diswall, M., Angstrom, J., Breimer, M. E., Goddeeris, B., Cox, E. & Teneberg, S. (2009). Recognition of blood group ABH type 1 determinants by the FedF adhesin of F18-fimbriated Escherichia coli. J Biol Chem 284, 9713-26.</ref> and CfaE on CFA/I pili<ref>Poole, S. T., McVeigh, A. L., Anantha, R. P., Lee, L. H., Akay, Y. M., Pontzer, E. A., Scott, D. A., Bullitt, E. & Savarino, S. J. (2007). Donor strand complementation governs intersubunit interaction of fimbriae of the alternate chaperone pathway. Mol Microbiol 63, 1372-84.</ref>) ) and uropathogenic ones (FimH on type 1 fimbriae<ref>Bouckaert, J., Berglund, J., Schembri, M., De Gents, E., Cools, L., Wuhrer, M., Hung, C.-S., Pinkner, J., Slättegard, R., Savialov, A., Choudhury, D., Langermann, S., Hultgren, S. J., Wyns, L., Klemm, P., Oscarson, S., Knight, S. D. & De Greve, H. (2005). Receptor binding studies disclose a novel class of high-affinity inhibitors of the Escherichia coli FimH adhesin. Mol. Microb. 55, 441-455.</ref> and PapG on P-pili<ref>Dodson, K. W., Pinkner, J. S., Rose, T., Magnusson, G., Hultgren, S. J. & Waksman, G. (2001). Structural basis of the interaction of the pyelonephritic E. coli adhesin to ist human kideny receptor. Cell 105, 733-743.</ref>). Fimbrial adhesins from other organisms, such as CupB6 from ''Pseudomonas aeruginosa'' are also investigated. All share the immunoglobulin-like fold of the two structural components, despite lack of any sequence identity and diversity in carbohydrate specificity and binding site, and the corresponding pili are assembled by the chaperone-usher pathway<ref>De Greve, H., Wyns, L. & Bouckaert, J. (2007). Combining sites of bacterial fimbriae. Curr Opin Struct Biol 17, 506-12.</ref><ref>Sauer, F. G., Barnhart, M., Choudhury, D., Knight, S. D., Waksman, G. & Hultgren, S. J. (2000). Chaperone-assisted pilus assembly and bacterial attachment. Curr Opin Struct Biol 10, 548-56.</ref>. The paradigm is unique among TAD for his specificity toward GlcNAc. The binding site is located laterally and not at the tip of the pili, therefore the long and flexible F17 fimbriae could intrude between the microvilli of the epithelium, with the binding site of the lectin domain interacting laterally with GlcNAc-containing receptors. Five naturally occurring variants, differing in 1-18 amino acids of the adhesion domain have been identified<ref>De Kerpel, M., Van Molle, I., Brys, L., Wyns, L., De Greve, H. & Bouckaert, J. (2006). N-terminal truncation enables crystallization of the receptor-binding domain of the FedF bacterial adhesin. Acta Crystallogr Sect F Struct Biol Cryst Commun 62, 1278-82.</ref>.

== CFG Participating Investigators contributing to the understanding of this paradigm ==
This is an emerging field of investigation and contributions arose from a small number of CFG Participating Investigators (PIs). These include: Esther Bullit, Eric Cox, Anne Imberty, Remy Loris, James Nataro

== Progress toward understanding this GBP paradigm ==

=== Carbohydrate ligands ===

The F17G adhesin is most specific for the disaccharide GlcNAcb1,3Gal that can be recognised as a terminal or internal sequence in bovine glycophorin <ref>Mouricout, M., Milhavet, M., Durié, C., Grange, P. Characterization of glycoprotein glycan receptors for Escherichia coli F17 fimbrial lectin, Microb. Pathog. (1995) 18, 297-306</ref>:
 
[[File:carbSynthe_0691_D000.jpg]]
 
The branched form gives a closely similar fluorescent signal:
 
[[File:carbSynthe_0897_D000.jpg]]
 
The presence of the b1,3 linkage of N-acetyl glucosamine to galactose enhances the affinity for F17G at least 2-fold, compared to the monosaccharide N-acetyl glucosamine, as validated using surface plasmon resonance measurements. Second best binders are the b1,4 and b1,6 galactose linked disaccharides, whereas chitobiose that is also a characterized inhibitor of F17G-mediated bacterial adhesion is clearly lagging behind. F17G can thus be ranked under glycan binding proteins that display high selectivity.

=== Cellular expression of GBP and ligands ===

F17G adhesins are constitutively expressed on enterotoxigenic E. coli infecting neonatal lambs, calves, and goat kids.

=== Biosynthesis of ligands ===
 
The F17G ligand GlcNAcb1,3Gal occurs universally but internally in polylactosaminyl glycans and in blood group antigens, both which are widely expressed on mamalian cell surfaces.
F17-fimbriated E. coli predominantly colonize neonatal animals but also cause mastitis in bovine mammae<ref>Lipman, L.J.A., de Nijs A., Gaastra W.. Isolation and identification of fimbriae and toxin production by Escherichia coli strains from cows with clinical mastitis, Vet. Microbiology 47 (1995) p. 1-7 </ref> producing the milk that protects the calves against bacterial infections. The N-acetyl glucosamine residue of GlcNAcb1,3Gal may still be unsubstituted at this early life stage, congruent the glycans recognized by F17G on the glycan array.

=== Structure ===

The F17G adhesin is a two-domain adhesin (TDA) located at the F17 fimbrial tip. The determination of the crystal structure of the F17G lectin domain led to the discovery of the variable immunoglobulin-like structure
as a paradigm for bacterial fimbrial TDAs <ref name=" Buts, L2003">
</ref>. F17G has a shallow groove for carbohydrate recognition on its flank.

 
[[File:F17G_Igfold.jpg]]
 

=== Biological roles of GBP-ligand interaction ===

The F17G fimbrial lectin enhances intestinal colonization in the early life of ruminants. The long and flexible F17 fimbriae can penetrate deep between intestinal microvilli, where the fimbrial tip adhesin finds its glycan receptors. The subsequent secretion of heat stable and heat lable toxins can lead to severe diarhea.

== CFG resources used in investigations ==
The best examples of CFG contributions to this paradigm are described below, with links to specific data sets. For a complete list of CFG data and resources relating to this paradigm, see the CFG database search results for [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=fimbriae&maxresults=20 fimbriae] and [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=pili&maxresults=20 pili].

=== Glycan profiling ===

 
=== Glycogene microarray ===

 
=== Knockout mouse lines ===

 
=== Glycan array ===
F17G adhesins have been screened for their glycan specificity (click [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_PA_v2_177_11182005 here]). To see all glycan array results for F17G adhesin, click [http://www.functionalglycomics.org/glycomics/search/jsp/result.jsp?query=F17G&cat=coreh here].

== Related GBPs ==
FedF, CfaE, FimH, PapG, CupB6

The specificity of some of the other fimbrial tip adhesins was determined by CFG glycan array analysis ([http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_2358 ''P. gingivalis'' fimbriae], [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_PA_v2_178_11182005 ''E. coli'' FedF adhesin], [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_1106 ''E. coli'' CfaE adhesin from CFA/I pili])

== References ==
<references/>

== Acknowledgements ==
The CFG is grateful to the following PIs for their contributions to this wiki page: Alisdair Boraston, Julie Bouckaert, Anne Imberty

F17G/GafD

2010-07-29T05:38:57Z

Julie Bouckaert: /* Biosynthesis of ligands */

The F17-G (GafD) adhesin at the tip of flexible F17 fimbriae of enterotoxigenic ''Escherichia coli'' mediates binding to N-acetyl-β-D-glucosamine-presenting receptors on the microvilli of the intestinal epithelium of ruminants, leading to diarrhea or septicaemia. F17-G belong to two-domain adhesins (TDA)s consisting of a pilin domain and a lectin domain, both having an Ig-fold joined via a short interdomain linker
<ref name=" Buts, L2003">
Buts, L., Bouckaert, J., De Gents, E., Loris, R., Oscarson, S., Lahmann, M., Messens, J., Brosens, E., Wyns, L. & De Greve, H. (2003). The fimbrial adhesin F17-G of enterotoxigenic Escherichia coli has an immunoglobulin-like lectin domain that binds N-acetylglucosamine. Mol. Microb. 49, 705-715.</ref><ref>Merckel, M. C., Tanskanen, J., Edelman, S., Westerlund-Wilkström, B., Korhonen, T. K. & Goldman, A. (2003). The structural basis of receptor-binding by Escherichia coli associaed with diarrhea and septicemia. J. Mol. Biol. 331, 897-905.</ref>. Related adhesins have been characterized in enteropathogenic ''E. coli'' ( FedF on F18 fimbriae<ref>Coddens, A., Diswall, M., Angstrom, J., Breimer, M. E., Goddeeris, B., Cox, E. & Teneberg, S. (2009). Recognition of blood group ABH type 1 determinants by the FedF adhesin of F18-fimbriated Escherichia coli. J Biol Chem 284, 9713-26.</ref> and CfaE on CFA/I pili<ref>Poole, S. T., McVeigh, A. L., Anantha, R. P., Lee, L. H., Akay, Y. M., Pontzer, E. A., Scott, D. A., Bullitt, E. & Savarino, S. J. (2007). Donor strand complementation governs intersubunit interaction of fimbriae of the alternate chaperone pathway. Mol Microbiol 63, 1372-84.</ref>) ) and uropathogenic ones (FimH on type 1 fimbriae<ref>Bouckaert, J., Berglund, J., Schembri, M., De Gents, E., Cools, L., Wuhrer, M., Hung, C.-S., Pinkner, J., Slättegard, R., Savialov, A., Choudhury, D., Langermann, S., Hultgren, S. J., Wyns, L., Klemm, P., Oscarson, S., Knight, S. D. & De Greve, H. (2005). Receptor binding studies disclose a novel class of high-affinity inhibitors of the Escherichia coli FimH adhesin. Mol. Microb. 55, 441-455.</ref> and PapG on P-pili<ref>Dodson, K. W., Pinkner, J. S., Rose, T., Magnusson, G., Hultgren, S. J. & Waksman, G. (2001). Structural basis of the interaction of the pyelonephritic E. coli adhesin to ist human kideny receptor. Cell 105, 733-743.</ref>). Fimbrial adhesins from other organisms, such as CupB6 from ''Pseudomonas aeruginosa'' are also investigated. All share the immunoglobulin-like fold of the two structural components, despite lack of any sequence identity and diversity in carbohydrate specificity and binding site, and the corresponding pili are assembled by the chaperone-usher pathway<ref>De Greve, H., Wyns, L. & Bouckaert, J. (2007). Combining sites of bacterial fimbriae. Curr Opin Struct Biol 17, 506-12.</ref><ref>Sauer, F. G., Barnhart, M., Choudhury, D., Knight, S. D., Waksman, G. & Hultgren, S. J. (2000). Chaperone-assisted pilus assembly and bacterial attachment. Curr Opin Struct Biol 10, 548-56.</ref>. The paradigm is unique among TAD for his specificity toward GlcNAc. The binding site is located laterally and not at the tip of the pili, therefore the long and flexible F17 fimbriae could intrude between the microvilli of the epithelium, with the binding site of the lectin domain interacting laterally with GlcNAc-containing receptors. Five naturally occurring variants, differing in 1-18 amino acids of the adhesion domain have been identified<ref>De Kerpel, M., Van Molle, I., Brys, L., Wyns, L., De Greve, H. & Bouckaert, J. (2006). N-terminal truncation enables crystallization of the receptor-binding domain of the FedF bacterial adhesin. Acta Crystallogr Sect F Struct Biol Cryst Commun 62, 1278-82.</ref>.

== CFG Participating Investigators contributing to the understanding of this paradigm ==
This is an emerging field of investigation and contributions arose from a small number of CFG Participating Investigators (PIs). These include: Esther Bullit, Eric Cox, Anne Imberty, Remy Loris, James Nataro

== Progress toward understanding this GBP paradigm ==

=== Carbohydrate ligands ===

The F17G adhesin is most specific for the disaccharide GlcNAcb1,3Gal that can be recognised as a terminal or internal sequence in bovine glycophorin (<ref>Mouricout, M., Milhavet, M., Durié, C., Grange, P. Characterization of glycoprotein glycan receptors for Escherichia coli F17 fimbrial lectin, Microb. Pathog. (1995) 18, 297-306</ref>):
 
[[File:carbSynthe_0691_D000.jpg]]
 
The branched form gives a closely similar fluorescent signal:
 
[[File:carbSynthe_0897_D000.jpg]]
 
The presence of the b1,3 linkage of N-acetyl glucosamine to galactose enhances the affinity for F17G at least 2-fold, compared to the monosaccharide N-acetyl glucosamine, as validated using surface plasmon resonance measurements. Second best binders are the b1,4 and b1,6 galactose linked disaccharides, whereas chitobiose that is also a characterized inhibitor of F17G-mediated bacterial adhesion is clearly lagging behind. F17G can thus be ranked under glycan binding proteins that display high selectivity.

=== Cellular expression of GBP and ligands ===

F17G adhesins are constitutively expressed on enterotoxigenic E. coli infecting neonatal lambs, calves, and goat kids.

=== Biosynthesis of ligands ===
 
The F17G ligand GlcNAcb1,3Gal occurs universally but internally in polylactosaminyl glycans and in blood group antigens, both which are widely expressed on mamalian cell surfaces.
F17-fimbriated E. coli predominantly colonize neonatal animals but also cause mastitis in bovine mammae<ref>Lipman, L.J.A., de Nijs A., Gaastra W.. Isolation and identification of fimbriae and toxin production by Escherichia coli strains from cows with clinical mastitis, Vet. Microbiology 47 (1995) p. 1-7 </ref> producing the milk that protects the calves against bacterial infections. The N-acetyl glucosamine residue of GlcNAcb1,3Gal may still be unsubstituted at this early life stage, congruent the glycans recognized by F17G on the glycan array.

=== Structure ===

The F17G adhesin is a two-domain adhesin (TDA) located at the F17 fimbrial tip. The determination of the crystal structure of the F17G lectin domain led to the discovery of the variable immunoglobulin-like structure
as a paradigm for bacterial fimbrial TDAs <ref name=" Buts, L2003">
</ref>. F17G has a shallow groove for carbohydrate recognition on its flank.

 
[[File:F17G_Igfold.jpg]]
 

=== Biological roles of GBP-ligand interaction ===

The F17G fimbrial lectin enhances intestinal colonization in the early life of ruminants. The long and flexible F17 fimbriae can penetrate deep between intestinal microvilli, where the fimbrial tip adhesin finds its glycan receptors. The subsequent secretion of heat stable and heat lable toxins can lead to severe diarhea.

== CFG resources used in investigations ==
The best examples of CFG contributions to this paradigm are described below, with links to specific data sets. For a complete list of CFG data and resources relating to this paradigm, see the CFG database search results for [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=fimbriae&maxresults=20 fimbriae] and [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=pili&maxresults=20 pili].

=== Glycan profiling ===

 
=== Glycogene microarray ===

 
=== Knockout mouse lines ===

 
=== Glycan array ===
F17G adhesins have been screened for their glycan specificity (click [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_PA_v2_177_11182005 here]). To see all glycan array results for F17G adhesin, click [http://www.functionalglycomics.org/glycomics/search/jsp/result.jsp?query=F17G&cat=coreh here].

== Related GBPs ==
FedF, CfaE, FimH, PapG, CupB6

The specificity of some of the other fimbrial tip adhesins was determined by CFG glycan array analysis ([http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_2358 ''P. gingivalis'' fimbriae], [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_PA_v2_178_11182005 ''E. coli'' FedF adhesin], [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_1106 ''E. coli'' CfaE adhesin from CFA/I pili])

== References ==
<references/>

== Acknowledgements ==
The CFG is grateful to the following PIs for their contributions to this wiki page: Alisdair Boraston, Julie Bouckaert, Anne Imberty

F17G/GafD

2010-07-29T05:38:06Z

Julie Bouckaert: /* Biosynthesis of ligands */

The F17-G (GafD) adhesin at the tip of flexible F17 fimbriae of enterotoxigenic ''Escherichia coli'' mediates binding to N-acetyl-β-D-glucosamine-presenting receptors on the microvilli of the intestinal epithelium of ruminants, leading to diarrhea or septicaemia. F17-G belong to two-domain adhesins (TDA)s consisting of a pilin domain and a lectin domain, both having an Ig-fold joined via a short interdomain linker
<ref name=" Buts, L2003">
Buts, L., Bouckaert, J., De Gents, E., Loris, R., Oscarson, S., Lahmann, M., Messens, J., Brosens, E., Wyns, L. & De Greve, H. (2003). The fimbrial adhesin F17-G of enterotoxigenic Escherichia coli has an immunoglobulin-like lectin domain that binds N-acetylglucosamine. Mol. Microb. 49, 705-715.</ref><ref>Merckel, M. C., Tanskanen, J., Edelman, S., Westerlund-Wilkström, B., Korhonen, T. K. & Goldman, A. (2003). The structural basis of receptor-binding by Escherichia coli associaed with diarrhea and septicemia. J. Mol. Biol. 331, 897-905.</ref>. Related adhesins have been characterized in enteropathogenic ''E. coli'' ( FedF on F18 fimbriae<ref>Coddens, A., Diswall, M., Angstrom, J., Breimer, M. E., Goddeeris, B., Cox, E. & Teneberg, S. (2009). Recognition of blood group ABH type 1 determinants by the FedF adhesin of F18-fimbriated Escherichia coli. J Biol Chem 284, 9713-26.</ref> and CfaE on CFA/I pili<ref>Poole, S. T., McVeigh, A. L., Anantha, R. P., Lee, L. H., Akay, Y. M., Pontzer, E. A., Scott, D. A., Bullitt, E. & Savarino, S. J. (2007). Donor strand complementation governs intersubunit interaction of fimbriae of the alternate chaperone pathway. Mol Microbiol 63, 1372-84.</ref>) ) and uropathogenic ones (FimH on type 1 fimbriae<ref>Bouckaert, J., Berglund, J., Schembri, M., De Gents, E., Cools, L., Wuhrer, M., Hung, C.-S., Pinkner, J., Slättegard, R., Savialov, A., Choudhury, D., Langermann, S., Hultgren, S. J., Wyns, L., Klemm, P., Oscarson, S., Knight, S. D. & De Greve, H. (2005). Receptor binding studies disclose a novel class of high-affinity inhibitors of the Escherichia coli FimH adhesin. Mol. Microb. 55, 441-455.</ref> and PapG on P-pili<ref>Dodson, K. W., Pinkner, J. S., Rose, T., Magnusson, G., Hultgren, S. J. & Waksman, G. (2001). Structural basis of the interaction of the pyelonephritic E. coli adhesin to ist human kideny receptor. Cell 105, 733-743.</ref>). Fimbrial adhesins from other organisms, such as CupB6 from ''Pseudomonas aeruginosa'' are also investigated. All share the immunoglobulin-like fold of the two structural components, despite lack of any sequence identity and diversity in carbohydrate specificity and binding site, and the corresponding pili are assembled by the chaperone-usher pathway<ref>De Greve, H., Wyns, L. & Bouckaert, J. (2007). Combining sites of bacterial fimbriae. Curr Opin Struct Biol 17, 506-12.</ref><ref>Sauer, F. G., Barnhart, M., Choudhury, D., Knight, S. D., Waksman, G. & Hultgren, S. J. (2000). Chaperone-assisted pilus assembly and bacterial attachment. Curr Opin Struct Biol 10, 548-56.</ref>. The paradigm is unique among TAD for his specificity toward GlcNAc. The binding site is located laterally and not at the tip of the pili, therefore the long and flexible F17 fimbriae could intrude between the microvilli of the epithelium, with the binding site of the lectin domain interacting laterally with GlcNAc-containing receptors. Five naturally occurring variants, differing in 1-18 amino acids of the adhesion domain have been identified<ref>De Kerpel, M., Van Molle, I., Brys, L., Wyns, L., De Greve, H. & Bouckaert, J. (2006). N-terminal truncation enables crystallization of the receptor-binding domain of the FedF bacterial adhesin. Acta Crystallogr Sect F Struct Biol Cryst Commun 62, 1278-82.</ref>.

== CFG Participating Investigators contributing to the understanding of this paradigm ==
This is an emerging field of investigation and contributions arose from a small number of CFG Participating Investigators (PIs). These include: Esther Bullit, Eric Cox, Anne Imberty, Remy Loris, James Nataro

== Progress toward understanding this GBP paradigm ==

=== Carbohydrate ligands ===

The F17G adhesin is most specific for the disaccharide GlcNAcb1,3Gal that can be recognised as a terminal or internal sequence in bovine glycophorin (<ref>Mouricout, M., Milhavet, M., Durié, C., Grange, P. Characterization of glycoprotein glycan receptors for Escherichia coli F17 fimbrial lectin, Microb. Pathog. (1995) 18, 297-306</ref>):
 
[[File:carbSynthe_0691_D000.jpg]]
 
The branched form gives a closely similar fluorescent signal:
 
[[File:carbSynthe_0897_D000.jpg]]
 
The presence of the b1,3 linkage of N-acetyl glucosamine to galactose enhances the affinity for F17G at least 2-fold, compared to the monosaccharide N-acetyl glucosamine, as validated using surface plasmon resonance measurements. Second best binders are the b1,4 and b1,6 galactose linked disaccharides, whereas chitobiose that is also a characterized inhibitor of F17G-mediated bacterial adhesion is clearly lagging behind. F17G can thus be ranked under glycan binding proteins that display high selectivity.

=== Cellular expression of GBP and ligands ===

F17G adhesins are constitutively expressed on enterotoxigenic E. coli infecting neonatal lambs, calves, and goat kids.

=== Biosynthesis of ligands ===
 
The F17G ligand GlcNAcb1,3Gal occurs universally but internally in polylactosaminyl glycans and in blood group antigens, both which are widely expressed on mamalian cell surfaces.
F17-fimbriated E. coli predominantly colonize neonatal animals but also cause mastitis in bovine mammae<ref>Lipman, L.J.A., de Nijs A., Gaastra W.. Isolation and identification of fimbriae and toxin production by Escherichia coli strains from cows with clinical mastitis, Vet. Microbiology 47 (1995) p. 1-7 </ref> (producing the milk that protects the calves against bacterial infections).
The N-acetyl glucosamine residue of GlcNAcb1,3Gal may still be unsubstituted at this early life stage, congruent the glycans recognized by F17G on the glycan array.

=== Structure ===

The F17G adhesin is a two-domain adhesin (TDA) located at the F17 fimbrial tip. The determination of the crystal structure of the F17G lectin domain led to the discovery of the variable immunoglobulin-like structure
as a paradigm for bacterial fimbrial TDAs <ref name=" Buts, L2003">
</ref>. F17G has a shallow groove for carbohydrate recognition on its flank.

 
[[File:F17G_Igfold.jpg]]
 

=== Biological roles of GBP-ligand interaction ===

The F17G fimbrial lectin enhances intestinal colonization in the early life of ruminants. The long and flexible F17 fimbriae can penetrate deep between intestinal microvilli, where the fimbrial tip adhesin finds its glycan receptors. The subsequent secretion of heat stable and heat lable toxins can lead to severe diarhea.

== CFG resources used in investigations ==
The best examples of CFG contributions to this paradigm are described below, with links to specific data sets. For a complete list of CFG data and resources relating to this paradigm, see the CFG database search results for [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=fimbriae&maxresults=20 fimbriae] and [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=pili&maxresults=20 pili].

=== Glycan profiling ===

 
=== Glycogene microarray ===

 
=== Knockout mouse lines ===

 
=== Glycan array ===
F17G adhesins have been screened for their glycan specificity (click [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_PA_v2_177_11182005 here]). To see all glycan array results for F17G adhesin, click [http://www.functionalglycomics.org/glycomics/search/jsp/result.jsp?query=F17G&cat=coreh here].

== Related GBPs ==
FedF, CfaE, FimH, PapG, CupB6

The specificity of some of the other fimbrial tip adhesins was determined by CFG glycan array analysis ([http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_2358 ''P. gingivalis'' fimbriae], [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_PA_v2_178_11182005 ''E. coli'' FedF adhesin], [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_1106 ''E. coli'' CfaE adhesin from CFA/I pili])

== References ==
<references/>

== Acknowledgements ==
The CFG is grateful to the following PIs for their contributions to this wiki page: Alisdair Boraston, Julie Bouckaert, Anne Imberty

F17G/GafD

2010-07-29T05:37:14Z

Julie Bouckaert: /* Biosynthesis of ligands */

The F17-G (GafD) adhesin at the tip of flexible F17 fimbriae of enterotoxigenic ''Escherichia coli'' mediates binding to N-acetyl-β-D-glucosamine-presenting receptors on the microvilli of the intestinal epithelium of ruminants, leading to diarrhea or septicaemia. F17-G belong to two-domain adhesins (TDA)s consisting of a pilin domain and a lectin domain, both having an Ig-fold joined via a short interdomain linker
<ref name=" Buts, L2003">
Buts, L., Bouckaert, J., De Gents, E., Loris, R., Oscarson, S., Lahmann, M., Messens, J., Brosens, E., Wyns, L. & De Greve, H. (2003). The fimbrial adhesin F17-G of enterotoxigenic Escherichia coli has an immunoglobulin-like lectin domain that binds N-acetylglucosamine. Mol. Microb. 49, 705-715.</ref><ref>Merckel, M. C., Tanskanen, J., Edelman, S., Westerlund-Wilkström, B., Korhonen, T. K. & Goldman, A. (2003). The structural basis of receptor-binding by Escherichia coli associaed with diarrhea and septicemia. J. Mol. Biol. 331, 897-905.</ref>. Related adhesins have been characterized in enteropathogenic ''E. coli'' ( FedF on F18 fimbriae<ref>Coddens, A., Diswall, M., Angstrom, J., Breimer, M. E., Goddeeris, B., Cox, E. & Teneberg, S. (2009). Recognition of blood group ABH type 1 determinants by the FedF adhesin of F18-fimbriated Escherichia coli. J Biol Chem 284, 9713-26.</ref> and CfaE on CFA/I pili<ref>Poole, S. T., McVeigh, A. L., Anantha, R. P., Lee, L. H., Akay, Y. M., Pontzer, E. A., Scott, D. A., Bullitt, E. & Savarino, S. J. (2007). Donor strand complementation governs intersubunit interaction of fimbriae of the alternate chaperone pathway. Mol Microbiol 63, 1372-84.</ref>) ) and uropathogenic ones (FimH on type 1 fimbriae<ref>Bouckaert, J., Berglund, J., Schembri, M., De Gents, E., Cools, L., Wuhrer, M., Hung, C.-S., Pinkner, J., Slättegard, R., Savialov, A., Choudhury, D., Langermann, S., Hultgren, S. J., Wyns, L., Klemm, P., Oscarson, S., Knight, S. D. & De Greve, H. (2005). Receptor binding studies disclose a novel class of high-affinity inhibitors of the Escherichia coli FimH adhesin. Mol. Microb. 55, 441-455.</ref> and PapG on P-pili<ref>Dodson, K. W., Pinkner, J. S., Rose, T., Magnusson, G., Hultgren, S. J. & Waksman, G. (2001). Structural basis of the interaction of the pyelonephritic E. coli adhesin to ist human kideny receptor. Cell 105, 733-743.</ref>). Fimbrial adhesins from other organisms, such as CupB6 from ''Pseudomonas aeruginosa'' are also investigated. All share the immunoglobulin-like fold of the two structural components, despite lack of any sequence identity and diversity in carbohydrate specificity and binding site, and the corresponding pili are assembled by the chaperone-usher pathway<ref>De Greve, H., Wyns, L. & Bouckaert, J. (2007). Combining sites of bacterial fimbriae. Curr Opin Struct Biol 17, 506-12.</ref><ref>Sauer, F. G., Barnhart, M., Choudhury, D., Knight, S. D., Waksman, G. & Hultgren, S. J. (2000). Chaperone-assisted pilus assembly and bacterial attachment. Curr Opin Struct Biol 10, 548-56.</ref>. The paradigm is unique among TAD for his specificity toward GlcNAc. The binding site is located laterally and not at the tip of the pili, therefore the long and flexible F17 fimbriae could intrude between the microvilli of the epithelium, with the binding site of the lectin domain interacting laterally with GlcNAc-containing receptors. Five naturally occurring variants, differing in 1-18 amino acids of the adhesion domain have been identified<ref>De Kerpel, M., Van Molle, I., Brys, L., Wyns, L., De Greve, H. & Bouckaert, J. (2006). N-terminal truncation enables crystallization of the receptor-binding domain of the FedF bacterial adhesin. Acta Crystallogr Sect F Struct Biol Cryst Commun 62, 1278-82.</ref>.

== CFG Participating Investigators contributing to the understanding of this paradigm ==
This is an emerging field of investigation and contributions arose from a small number of CFG Participating Investigators (PIs). These include: Esther Bullit, Eric Cox, Anne Imberty, Remy Loris, James Nataro

== Progress toward understanding this GBP paradigm ==

=== Carbohydrate ligands ===

The F17G adhesin is most specific for the disaccharide GlcNAcb1,3Gal that can be recognised as a terminal or internal sequence in bovine glycophorin (<ref>Mouricout, M., Milhavet, M., Durié, C., Grange, P. Characterization of glycoprotein glycan receptors for Escherichia coli F17 fimbrial lectin, Microb. Pathog. (1995) 18, 297-306</ref>):
 
[[File:carbSynthe_0691_D000.jpg]]
 
The branched form gives a closely similar fluorescent signal:
 
[[File:carbSynthe_0897_D000.jpg]]
 
The presence of the b1,3 linkage of N-acetyl glucosamine to galactose enhances the affinity for F17G at least 2-fold, compared to the monosaccharide N-acetyl glucosamine, as validated using surface plasmon resonance measurements. Second best binders are the b1,4 and b1,6 galactose linked disaccharides, whereas chitobiose that is also a characterized inhibitor of F17G-mediated bacterial adhesion is clearly lagging behind. F17G can thus be ranked under glycan binding proteins that display high selectivity.

=== Cellular expression of GBP and ligands ===

F17G adhesins are constitutively expressed on enterotoxigenic E. coli infecting neonatal lambs, calves, and goat kids.

=== Biosynthesis of ligands ===
 
The F17G ligand GlcNAcb1,3Gal occurs universally but internally in polylactosaminyl glycans and in blood group antigens, both which are widely expressed on mamalian cell surfaces.
F17-fimbriated E. coli predominantly colonize neonatal animals but also cause mastitis in bovine mammae<ref>Lipman LJA, de Nijs A, Gaastra W. Isolation and identification of fimbriae and toxin production by Escherichia coli strains from cows with clinical mastitis Vet. Microbiology 47 (1995) p. 1-7 </ref> (producing the milk that protects the calves against bacterial infections).
The N-acetyl glucosamine residue of GlcNAcb1,3Gal may still be unsubstituted at this early life stage, congruent the glycans recognized by F17G on the glycan array.

=== Structure ===

The F17G adhesin is a two-domain adhesin (TDA) located at the F17 fimbrial tip. The determination of the crystal structure of the F17G lectin domain led to the discovery of the variable immunoglobulin-like structure
as a paradigm for bacterial fimbrial TDAs <ref name=" Buts, L2003">
</ref>. F17G has a shallow groove for carbohydrate recognition on its flank.

 
[[File:F17G_Igfold.jpg]]
 

=== Biological roles of GBP-ligand interaction ===

The F17G fimbrial lectin enhances intestinal colonization in the early life of ruminants. The long and flexible F17 fimbriae can penetrate deep between intestinal microvilli, where the fimbrial tip adhesin finds its glycan receptors. The subsequent secretion of heat stable and heat lable toxins can lead to severe diarhea.

== CFG resources used in investigations ==
The best examples of CFG contributions to this paradigm are described below, with links to specific data sets. For a complete list of CFG data and resources relating to this paradigm, see the CFG database search results for [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=fimbriae&maxresults=20 fimbriae] and [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=pili&maxresults=20 pili].

=== Glycan profiling ===

 
=== Glycogene microarray ===

 
=== Knockout mouse lines ===

 
=== Glycan array ===
F17G adhesins have been screened for their glycan specificity (click [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_PA_v2_177_11182005 here]). To see all glycan array results for F17G adhesin, click [http://www.functionalglycomics.org/glycomics/search/jsp/result.jsp?query=F17G&cat=coreh here].

== Related GBPs ==
FedF, CfaE, FimH, PapG, CupB6

The specificity of some of the other fimbrial tip adhesins was determined by CFG glycan array analysis ([http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_2358 ''P. gingivalis'' fimbriae], [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_PA_v2_178_11182005 ''E. coli'' FedF adhesin], [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_1106 ''E. coli'' CfaE adhesin from CFA/I pili])

== References ==
<references/>

== Acknowledgements ==
The CFG is grateful to the following PIs for their contributions to this wiki page: Alisdair Boraston, Julie Bouckaert, Anne Imberty

F17G/GafD

2010-07-29T05:35:26Z

Julie Bouckaert: /* Biosynthesis of ligands */

The F17-G (GafD) adhesin at the tip of flexible F17 fimbriae of enterotoxigenic ''Escherichia coli'' mediates binding to N-acetyl-β-D-glucosamine-presenting receptors on the microvilli of the intestinal epithelium of ruminants, leading to diarrhea or septicaemia. F17-G belong to two-domain adhesins (TDA)s consisting of a pilin domain and a lectin domain, both having an Ig-fold joined via a short interdomain linker
<ref name=" Buts, L2003">
Buts, L., Bouckaert, J., De Gents, E., Loris, R., Oscarson, S., Lahmann, M., Messens, J., Brosens, E., Wyns, L. & De Greve, H. (2003). The fimbrial adhesin F17-G of enterotoxigenic Escherichia coli has an immunoglobulin-like lectin domain that binds N-acetylglucosamine. Mol. Microb. 49, 705-715.</ref><ref>Merckel, M. C., Tanskanen, J., Edelman, S., Westerlund-Wilkström, B., Korhonen, T. K. & Goldman, A. (2003). The structural basis of receptor-binding by Escherichia coli associaed with diarrhea and septicemia. J. Mol. Biol. 331, 897-905.</ref>. Related adhesins have been characterized in enteropathogenic ''E. coli'' ( FedF on F18 fimbriae<ref>Coddens, A., Diswall, M., Angstrom, J., Breimer, M. E., Goddeeris, B., Cox, E. & Teneberg, S. (2009). Recognition of blood group ABH type 1 determinants by the FedF adhesin of F18-fimbriated Escherichia coli. J Biol Chem 284, 9713-26.</ref> and CfaE on CFA/I pili<ref>Poole, S. T., McVeigh, A. L., Anantha, R. P., Lee, L. H., Akay, Y. M., Pontzer, E. A., Scott, D. A., Bullitt, E. & Savarino, S. J. (2007). Donor strand complementation governs intersubunit interaction of fimbriae of the alternate chaperone pathway. Mol Microbiol 63, 1372-84.</ref>) ) and uropathogenic ones (FimH on type 1 fimbriae<ref>Bouckaert, J., Berglund, J., Schembri, M., De Gents, E., Cools, L., Wuhrer, M., Hung, C.-S., Pinkner, J., Slättegard, R., Savialov, A., Choudhury, D., Langermann, S., Hultgren, S. J., Wyns, L., Klemm, P., Oscarson, S., Knight, S. D. & De Greve, H. (2005). Receptor binding studies disclose a novel class of high-affinity inhibitors of the Escherichia coli FimH adhesin. Mol. Microb. 55, 441-455.</ref> and PapG on P-pili<ref>Dodson, K. W., Pinkner, J. S., Rose, T., Magnusson, G., Hultgren, S. J. & Waksman, G. (2001). Structural basis of the interaction of the pyelonephritic E. coli adhesin to ist human kideny receptor. Cell 105, 733-743.</ref>). Fimbrial adhesins from other organisms, such as CupB6 from ''Pseudomonas aeruginosa'' are also investigated. All share the immunoglobulin-like fold of the two structural components, despite lack of any sequence identity and diversity in carbohydrate specificity and binding site, and the corresponding pili are assembled by the chaperone-usher pathway<ref>De Greve, H., Wyns, L. & Bouckaert, J. (2007). Combining sites of bacterial fimbriae. Curr Opin Struct Biol 17, 506-12.</ref><ref>Sauer, F. G., Barnhart, M., Choudhury, D., Knight, S. D., Waksman, G. & Hultgren, S. J. (2000). Chaperone-assisted pilus assembly and bacterial attachment. Curr Opin Struct Biol 10, 548-56.</ref>. The paradigm is unique among TAD for his specificity toward GlcNAc. The binding site is located laterally and not at the tip of the pili, therefore the long and flexible F17 fimbriae could intrude between the microvilli of the epithelium, with the binding site of the lectin domain interacting laterally with GlcNAc-containing receptors. Five naturally occurring variants, differing in 1-18 amino acids of the adhesion domain have been identified<ref>De Kerpel, M., Van Molle, I., Brys, L., Wyns, L., De Greve, H. & Bouckaert, J. (2006). N-terminal truncation enables crystallization of the receptor-binding domain of the FedF bacterial adhesin. Acta Crystallogr Sect F Struct Biol Cryst Commun 62, 1278-82.</ref>.

== CFG Participating Investigators contributing to the understanding of this paradigm ==
This is an emerging field of investigation and contributions arose from a small number of CFG Participating Investigators (PIs). These include: Esther Bullit, Eric Cox, Anne Imberty, Remy Loris, James Nataro

== Progress toward understanding this GBP paradigm ==

=== Carbohydrate ligands ===

The F17G adhesin is most specific for the disaccharide GlcNAcb1,3Gal that can be recognised as a terminal or internal sequence in bovine glycophorin (<ref>Mouricout, M., Milhavet, M., Durié, C., Grange, P. Characterization of glycoprotein glycan receptors for Escherichia coli F17 fimbrial lectin, Microb. Pathog. (1995) 18, 297-306</ref>):
 
[[File:carbSynthe_0691_D000.jpg]]
 
The branched form gives a closely similar fluorescent signal:
 
[[File:carbSynthe_0897_D000.jpg]]
 
The presence of the b1,3 linkage of N-acetyl glucosamine to galactose enhances the affinity for F17G at least 2-fold, compared to the monosaccharide N-acetyl glucosamine, as validated using surface plasmon resonance measurements. Second best binders are the b1,4 and b1,6 galactose linked disaccharides, whereas chitobiose that is also a characterized inhibitor of F17G-mediated bacterial adhesion is clearly lagging behind. F17G can thus be ranked under glycan binding proteins that display high selectivity.

=== Cellular expression of GBP and ligands ===

F17G adhesins are constitutively expressed on enterotoxigenic E. coli infecting neonatal lambs, calves, and goat kids.

=== Biosynthesis of ligands ===
 
The F17G ligand GlcNAcb1,3Gal occurs universally but internally in polylactosaminyl glycans and in blood group antigens, both which are widely expressed on mamalian cell surfaces.
F17-fimbriated E. coli predominantly colonize neonatal animals but also cause mastitis in bovine mammae<ref>11</ref> (producing the milk that protects the calves against bacterial infections).
The N-acetyl glucosamine residue of GlcNAcb1,3Gal may still be unsubstituted at this early life stage, congruent the glycans recognized by F17G on the glycan array.

=== Structure ===

The F17G adhesin is a two-domain adhesin (TDA) located at the F17 fimbrial tip. The determination of the crystal structure of the F17G lectin domain led to the discovery of the variable immunoglobulin-like structure
as a paradigm for bacterial fimbrial TDAs <ref name=" Buts, L2003">
</ref>. F17G has a shallow groove for carbohydrate recognition on its flank.

 
[[File:F17G_Igfold.jpg]]
 

=== Biological roles of GBP-ligand interaction ===

The F17G fimbrial lectin enhances intestinal colonization in the early life of ruminants. The long and flexible F17 fimbriae can penetrate deep between intestinal microvilli, where the fimbrial tip adhesin finds its glycan receptors. The subsequent secretion of heat stable and heat lable toxins can lead to severe diarhea.

== CFG resources used in investigations ==
The best examples of CFG contributions to this paradigm are described below, with links to specific data sets. For a complete list of CFG data and resources relating to this paradigm, see the CFG database search results for [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=fimbriae&maxresults=20 fimbriae] and [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=pili&maxresults=20 pili].

=== Glycan profiling ===

 
=== Glycogene microarray ===

 
=== Knockout mouse lines ===

 
=== Glycan array ===
F17G adhesins have been screened for their glycan specificity (click [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_PA_v2_177_11182005 here]). To see all glycan array results for F17G adhesin, click [http://www.functionalglycomics.org/glycomics/search/jsp/result.jsp?query=F17G&cat=coreh here].

== Related GBPs ==
FedF, CfaE, FimH, PapG, CupB6

The specificity of some of the other fimbrial tip adhesins was determined by CFG glycan array analysis ([http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_2358 ''P. gingivalis'' fimbriae], [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_PA_v2_178_11182005 ''E. coli'' FedF adhesin], [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_1106 ''E. coli'' CfaE adhesin from CFA/I pili])

== References ==
<references/>

== Acknowledgements ==
The CFG is grateful to the following PIs for their contributions to this wiki page: Alisdair Boraston, Julie Bouckaert, Anne Imberty

F17G/GafD

2010-07-29T05:31:47Z

Julie Bouckaert: /* Biosynthesis of ligands */

The F17-G (GafD) adhesin at the tip of flexible F17 fimbriae of enterotoxigenic ''Escherichia coli'' mediates binding to N-acetyl-β-D-glucosamine-presenting receptors on the microvilli of the intestinal epithelium of ruminants, leading to diarrhea or septicaemia. F17-G belong to two-domain adhesins (TDA)s consisting of a pilin domain and a lectin domain, both having an Ig-fold joined via a short interdomain linker
<ref name=" Buts, L2003">
Buts, L., Bouckaert, J., De Gents, E., Loris, R., Oscarson, S., Lahmann, M., Messens, J., Brosens, E., Wyns, L. & De Greve, H. (2003). The fimbrial adhesin F17-G of enterotoxigenic Escherichia coli has an immunoglobulin-like lectin domain that binds N-acetylglucosamine. Mol. Microb. 49, 705-715.</ref><ref>Merckel, M. C., Tanskanen, J., Edelman, S., Westerlund-Wilkström, B., Korhonen, T. K. & Goldman, A. (2003). The structural basis of receptor-binding by Escherichia coli associaed with diarrhea and septicemia. J. Mol. Biol. 331, 897-905.</ref>. Related adhesins have been characterized in enteropathogenic ''E. coli'' ( FedF on F18 fimbriae<ref>Coddens, A., Diswall, M., Angstrom, J., Breimer, M. E., Goddeeris, B., Cox, E. & Teneberg, S. (2009). Recognition of blood group ABH type 1 determinants by the FedF adhesin of F18-fimbriated Escherichia coli. J Biol Chem 284, 9713-26.</ref> and CfaE on CFA/I pili<ref>Poole, S. T., McVeigh, A. L., Anantha, R. P., Lee, L. H., Akay, Y. M., Pontzer, E. A., Scott, D. A., Bullitt, E. & Savarino, S. J. (2007). Donor strand complementation governs intersubunit interaction of fimbriae of the alternate chaperone pathway. Mol Microbiol 63, 1372-84.</ref>) ) and uropathogenic ones (FimH on type 1 fimbriae<ref>Bouckaert, J., Berglund, J., Schembri, M., De Gents, E., Cools, L., Wuhrer, M., Hung, C.-S., Pinkner, J., Slättegard, R., Savialov, A., Choudhury, D., Langermann, S., Hultgren, S. J., Wyns, L., Klemm, P., Oscarson, S., Knight, S. D. & De Greve, H. (2005). Receptor binding studies disclose a novel class of high-affinity inhibitors of the Escherichia coli FimH adhesin. Mol. Microb. 55, 441-455.</ref> and PapG on P-pili<ref>Dodson, K. W., Pinkner, J. S., Rose, T., Magnusson, G., Hultgren, S. J. & Waksman, G. (2001). Structural basis of the interaction of the pyelonephritic E. coli adhesin to ist human kideny receptor. Cell 105, 733-743.</ref>). Fimbrial adhesins from other organisms, such as CupB6 from ''Pseudomonas aeruginosa'' are also investigated. All share the immunoglobulin-like fold of the two structural components, despite lack of any sequence identity and diversity in carbohydrate specificity and binding site, and the corresponding pili are assembled by the chaperone-usher pathway<ref>De Greve, H., Wyns, L. & Bouckaert, J. (2007). Combining sites of bacterial fimbriae. Curr Opin Struct Biol 17, 506-12.</ref><ref>Sauer, F. G., Barnhart, M., Choudhury, D., Knight, S. D., Waksman, G. & Hultgren, S. J. (2000). Chaperone-assisted pilus assembly and bacterial attachment. Curr Opin Struct Biol 10, 548-56.</ref>. The paradigm is unique among TAD for his specificity toward GlcNAc. The binding site is located laterally and not at the tip of the pili, therefore the long and flexible F17 fimbriae could intrude between the microvilli of the epithelium, with the binding site of the lectin domain interacting laterally with GlcNAc-containing receptors. Five naturally occurring variants, differing in 1-18 amino acids of the adhesion domain have been identified<ref>De Kerpel, M., Van Molle, I., Brys, L., Wyns, L., De Greve, H. & Bouckaert, J. (2006). N-terminal truncation enables crystallization of the receptor-binding domain of the FedF bacterial adhesin. Acta Crystallogr Sect F Struct Biol Cryst Commun 62, 1278-82.</ref>.

== CFG Participating Investigators contributing to the understanding of this paradigm ==
This is an emerging field of investigation and contributions arose from a small number of CFG Participating Investigators (PIs). These include: Esther Bullit, Eric Cox, Anne Imberty, Remy Loris, James Nataro

== Progress toward understanding this GBP paradigm ==

=== Carbohydrate ligands ===

The F17G adhesin is most specific for the disaccharide GlcNAcb1,3Gal that can be recognised as a terminal or internal sequence in bovine glycophorin (<ref>Mouricout, M., Milhavet, M., Durié, C., Grange, P. Characterization of glycoprotein glycan receptors for Escherichia coli F17 fimbrial lectin, Microb. Pathog. (1995) 18, 297-306</ref>):
 
[[File:carbSynthe_0691_D000.jpg]]
 
The branched form gives a closely similar fluorescent signal:
 
[[File:carbSynthe_0897_D000.jpg]]
 
The presence of the b1,3 linkage of N-acetyl glucosamine to galactose enhances the affinity for F17G at least 2-fold, compared to the monosaccharide N-acetyl glucosamine, as validated using surface plasmon resonance measurements. Second best binders are the b1,4 and b1,6 galactose linked disaccharides, whereas chitobiose that is also a characterized inhibitor of F17G-mediated bacterial adhesion is clearly lagging behind. F17G can thus be ranked under glycan binding proteins that display high selectivity.

=== Cellular expression of GBP and ligands ===

F17G adhesins are constitutively expressed on enterotoxigenic E. coli infecting neonatal lambs, calves, and goat kids.

=== Biosynthesis of ligands ===
 
The F17G ligand GlcNAcb1,3Gal occurs universally but internally in polylactosaminyl glycans and in blood group antigens, both which are widely expressed on mamalian cell surfaces.
F17-fimbriated E. coli predominantly colonize neonatal animals but also cause mastitis in bovine mammae (producing the milk that protects the calves against bacterial infections).
The N-acetyl glucosamine residue of GlcNAcb1,3Gal may still be unsubstituted at this early life stage, congruent with the glycans recognized by F17G on the glycan array.

=== Structure ===

The F17G adhesin is a two-domain adhesin (TDA) located at the F17 fimbrial tip. The determination of the crystal structure of the F17G lectin domain led to the discovery of the variable immunoglobulin-like structure
as a paradigm for bacterial fimbrial TDAs <ref name=" Buts, L2003">
</ref>. F17G has a shallow groove for carbohydrate recognition on its flank.

 
[[File:F17G_Igfold.jpg]]
 

=== Biological roles of GBP-ligand interaction ===

The F17G fimbrial lectin enhances intestinal colonization in the early life of ruminants. The long and flexible F17 fimbriae can penetrate deep between intestinal microvilli, where the fimbrial tip adhesin finds its glycan receptors. The subsequent secretion of heat stable and heat lable toxins can lead to severe diarhea.

== CFG resources used in investigations ==
The best examples of CFG contributions to this paradigm are described below, with links to specific data sets. For a complete list of CFG data and resources relating to this paradigm, see the CFG database search results for [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=fimbriae&maxresults=20 fimbriae] and [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=pili&maxresults=20 pili].

=== Glycan profiling ===

 
=== Glycogene microarray ===

 
=== Knockout mouse lines ===

 
=== Glycan array ===
F17G adhesins have been screened for their glycan specificity (click [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_PA_v2_177_11182005 here]). To see all glycan array results for F17G adhesin, click [http://www.functionalglycomics.org/glycomics/search/jsp/result.jsp?query=F17G&cat=coreh here].

== Related GBPs ==
FedF, CfaE, FimH, PapG, CupB6

The specificity of some of the other fimbrial tip adhesins was determined by CFG glycan array analysis ([http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_2358 ''P. gingivalis'' fimbriae], [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_PA_v2_178_11182005 ''E. coli'' FedF adhesin], [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_1106 ''E. coli'' CfaE adhesin from CFA/I pili])

== References ==
<references/>

== Acknowledgements ==
The CFG is grateful to the following PIs for their contributions to this wiki page: Alisdair Boraston, Julie Bouckaert, Anne Imberty

F17G/GafD

2010-07-28T17:12:31Z

Julie Bouckaert: /* Biosynthesis of ligands */

The F17-G (GafD) adhesin at the tip of flexible F17 fimbriae of enterotoxigenic ''Escherichia coli'' mediates binding to N-acetyl-β-D-glucosamine-presenting receptors on the microvilli of the intestinal epithelium of ruminants, leading to diarrhea or septicaemia. F17-G belong to two-domain adhesins (TDA)s consisting of a pilin domain and a lectin domain, both having an Ig-fold joined via a short interdomain linker
<ref name=" Buts, L2003">
Buts, L., Bouckaert, J., De Gents, E., Loris, R., Oscarson, S., Lahmann, M., Messens, J., Brosens, E., Wyns, L. & De Greve, H. (2003). The fimbrial adhesin F17-G of enterotoxigenic Escherichia coli has an immunoglobulin-like lectin domain that binds N-acetylglucosamine. Mol. Microb. 49, 705-715.</ref><ref>Merckel, M. C., Tanskanen, J., Edelman, S., Westerlund-Wilkström, B., Korhonen, T. K. & Goldman, A. (2003). The structural basis of receptor-binding by Escherichia coli associaed with diarrhea and septicemia. J. Mol. Biol. 331, 897-905.</ref>. Related adhesins have been characterized in enteropathogenic ''E. coli'' ( FedF on F18 fimbriae<ref>Coddens, A., Diswall, M., Angstrom, J., Breimer, M. E., Goddeeris, B., Cox, E. & Teneberg, S. (2009). Recognition of blood group ABH type 1 determinants by the FedF adhesin of F18-fimbriated Escherichia coli. J Biol Chem 284, 9713-26.</ref> and CfaE on CFA/I pili<ref>Poole, S. T., McVeigh, A. L., Anantha, R. P., Lee, L. H., Akay, Y. M., Pontzer, E. A., Scott, D. A., Bullitt, E. & Savarino, S. J. (2007). Donor strand complementation governs intersubunit interaction of fimbriae of the alternate chaperone pathway. Mol Microbiol 63, 1372-84.</ref>) ) and uropathogenic ones (FimH on type 1 fimbriae<ref>Bouckaert, J., Berglund, J., Schembri, M., De Gents, E., Cools, L., Wuhrer, M., Hung, C.-S., Pinkner, J., Slättegard, R., Savialov, A., Choudhury, D., Langermann, S., Hultgren, S. J., Wyns, L., Klemm, P., Oscarson, S., Knight, S. D. & De Greve, H. (2005). Receptor binding studies disclose a novel class of high-affinity inhibitors of the Escherichia coli FimH adhesin. Mol. Microb. 55, 441-455.</ref> and PapG on P-pili<ref>Dodson, K. W., Pinkner, J. S., Rose, T., Magnusson, G., Hultgren, S. J. & Waksman, G. (2001). Structural basis of the interaction of the pyelonephritic E. coli adhesin to ist human kideny receptor. Cell 105, 733-743.</ref>). Fimbrial adhesins from other organisms, such as CupB6 from ''Pseudomonas aeruginosa'' are also investigated. All share the immunoglobulin-like fold of the two structural components, despite lack of any sequence identity and diversity in carbohydrate specificity and binding site, and the corresponding pili are assembled by the chaperone-usher pathway<ref>De Greve, H., Wyns, L. & Bouckaert, J. (2007). Combining sites of bacterial fimbriae. Curr Opin Struct Biol 17, 506-12.</ref><ref>Sauer, F. G., Barnhart, M., Choudhury, D., Knight, S. D., Waksman, G. & Hultgren, S. J. (2000). Chaperone-assisted pilus assembly and bacterial attachment. Curr Opin Struct Biol 10, 548-56.</ref>. The paradigm is unique among TAD for his specificity toward GlcNAc. The binding site is located laterally and not at the tip of the pili, therefore the long and flexible F17 fimbriae could intrude between the microvilli of the epithelium, with the binding site of the lectin domain interacting laterally with GlcNAc-containing receptors. Five naturally occurring variants, differing in 1-18 amino acids of the adhesion domain have been identified<ref>De Kerpel, M., Van Molle, I., Brys, L., Wyns, L., De Greve, H. & Bouckaert, J. (2006). N-terminal truncation enables crystallization of the receptor-binding domain of the FedF bacterial adhesin. Acta Crystallogr Sect F Struct Biol Cryst Commun 62, 1278-82.</ref>.

== CFG Participating Investigators contributing to the understanding of this paradigm ==
This is an emerging field of investigation and contributions arose from a small number of CFG Participating Investigators (PIs). These include: Esther Bullit, Eric Cox, Anne Imberty, Remy Loris, James Nataro

== Progress toward understanding this GBP paradigm ==

=== Carbohydrate ligands ===

The F17G adhesin is most specific for the disaccharide GlcNAcb1,3Gal that can be recognised as a terminal or internal sequence in bovine glycophorin (<ref>Mouricout, M., Milhavet, M., Durié, C., Grange, P. Characterization of glycoprotein glycan receptors for Escherichia coli F17 fimbrial lectin, Microb. Pathog. (1995) 18, 297-306</ref>):
 
[[File:carbSynthe_0691_D000.jpg]]
 
The branched form gives a closely similar fluorescent signal:
 
[[File:carbSynthe_0897_D000.jpg]]
 
The presence of the b1,3 linkage of N-acetyl glucosamine to galactose enhances the affinity for F17G at least 2-fold, compared to the monosaccharide N-acetyl glucosamine, as validated using surface plasmon resonance measurements. Second best binders are the b1,4 and b1,6 galactose linked disaccharides, whereas chitobiose that is also a characterized inhibitor of F17G-mediated bacterial adhesion is clearly lagging behind. F17G can thus be ranked under glycan binding proteins that display high selectivity.

=== Cellular expression of GBP and ligands ===

F17G adhesins are constitutively expressed on enterotoxigenic E. coli infecting neonatal lambs, calves, and goat kids.

=== Biosynthesis of ligands ===
 
The F17G ligand GlcNAcb1,3Gal occurs universally in polylactosaminyl and in blood group antigens, both expressed widely
on mamalian cell surfaces. F17G only colonizes neonatal animals, which may indicate that the N-acetyl glucosamine residue is still unsubstituted at the non-reducing end at this early life stage. This is congruent with what F17G binds on the glycan array.

=== Structure ===

The F17G adhesin is a two-domain adhesin (TDA) located at the F17 fimbrial tip. The determination of the crystal structure of the F17G lectin domain led to the discovery of the variable immunoglobulin-like structure
as a paradigm for bacterial fimbrial TDAs <ref name=" Buts, L2003">
</ref>. F17G has a shallow groove for carbohydrate recognition on its flank.

 
[[File:F17G_Igfold.jpg]]
 

=== Biological roles of GBP-ligand interaction ===

The F17G fimbrial lectin enhances intestinal colonization in the early life of ruminants. The long and flexible F17 fimbriae can penetrate deep between intestinal microvilli, where the fimbrial tip adhesin finds its glycan receptors. The subsequent secretion of heat stable and heat lable toxins can lead to severe diarhea.

== CFG resources used in investigations ==
The best examples of CFG contributions to this paradigm are described below, with links to specific data sets. For a complete list of CFG data and resources relating to this paradigm, see the CFG database search results for [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=fimbriae&maxresults=20 fimbriae] and [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=pili&maxresults=20 pili].

=== Glycan profiling ===

 
=== Glycogene microarray ===

 
=== Knockout mouse lines ===

 
=== Glycan array ===
F17G adhesins have been screened for their glycan specificity (click [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_PA_v2_177_11182005 here]). To see all glycan array results for F17G adhesin, click [http://www.functionalglycomics.org/glycomics/search/jsp/result.jsp?query=F17G&cat=coreh here].

== Related GBPs ==
FedF, CfaE, FimH, PapG, CupB6

The specificity of some of the other fimbrial tip adhesins was determined by CFG glycan array analysis ([http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_2358 ''P. gingivalis'' fimbriae], [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_PA_v2_178_11182005 ''E. coli'' FedF adhesin], [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_1106 ''E. coli'' CfaE adhesin from CFA/I pili])

== References ==
<references/>

== Acknowledgements ==
The CFG is grateful to the following PIs for their contributions to this wiki page: Alisdair Boraston, Julie Bouckaert, Anne Imberty

F17G/GafD

2010-07-28T17:05:12Z

Julie Bouckaert: /* Carbohydrate ligands */

The F17-G (GafD) adhesin at the tip of flexible F17 fimbriae of enterotoxigenic ''Escherichia coli'' mediates binding to N-acetyl-β-D-glucosamine-presenting receptors on the microvilli of the intestinal epithelium of ruminants, leading to diarrhea or septicaemia. F17-G belong to two-domain adhesins (TDA)s consisting of a pilin domain and a lectin domain, both having an Ig-fold joined via a short interdomain linker
<ref name=" Buts, L2003">
Buts, L., Bouckaert, J., De Gents, E., Loris, R., Oscarson, S., Lahmann, M., Messens, J., Brosens, E., Wyns, L. & De Greve, H. (2003). The fimbrial adhesin F17-G of enterotoxigenic Escherichia coli has an immunoglobulin-like lectin domain that binds N-acetylglucosamine. Mol. Microb. 49, 705-715.</ref><ref>Merckel, M. C., Tanskanen, J., Edelman, S., Westerlund-Wilkström, B., Korhonen, T. K. & Goldman, A. (2003). The structural basis of receptor-binding by Escherichia coli associaed with diarrhea and septicemia. J. Mol. Biol. 331, 897-905.</ref>. Related adhesins have been characterized in enteropathogenic ''E. coli'' ( FedF on F18 fimbriae<ref>Coddens, A., Diswall, M., Angstrom, J., Breimer, M. E., Goddeeris, B., Cox, E. & Teneberg, S. (2009). Recognition of blood group ABH type 1 determinants by the FedF adhesin of F18-fimbriated Escherichia coli. J Biol Chem 284, 9713-26.</ref> and CfaE on CFA/I pili<ref>Poole, S. T., McVeigh, A. L., Anantha, R. P., Lee, L. H., Akay, Y. M., Pontzer, E. A., Scott, D. A., Bullitt, E. & Savarino, S. J. (2007). Donor strand complementation governs intersubunit interaction of fimbriae of the alternate chaperone pathway. Mol Microbiol 63, 1372-84.</ref>) ) and uropathogenic ones (FimH on type 1 fimbriae<ref>Bouckaert, J., Berglund, J., Schembri, M., De Gents, E., Cools, L., Wuhrer, M., Hung, C.-S., Pinkner, J., Slättegard, R., Savialov, A., Choudhury, D., Langermann, S., Hultgren, S. J., Wyns, L., Klemm, P., Oscarson, S., Knight, S. D. & De Greve, H. (2005). Receptor binding studies disclose a novel class of high-affinity inhibitors of the Escherichia coli FimH adhesin. Mol. Microb. 55, 441-455.</ref> and PapG on P-pili<ref>Dodson, K. W., Pinkner, J. S., Rose, T., Magnusson, G., Hultgren, S. J. & Waksman, G. (2001). Structural basis of the interaction of the pyelonephritic E. coli adhesin to ist human kideny receptor. Cell 105, 733-743.</ref>). Fimbrial adhesins from other organisms, such as CupB6 from ''Pseudomonas aeruginosa'' are also investigated. All share the immunoglobulin-like fold of the two structural components, despite lack of any sequence identity and diversity in carbohydrate specificity and binding site, and the corresponding pili are assembled by the chaperone-usher pathway<ref>De Greve, H., Wyns, L. & Bouckaert, J. (2007). Combining sites of bacterial fimbriae. Curr Opin Struct Biol 17, 506-12.</ref><ref>Sauer, F. G., Barnhart, M., Choudhury, D., Knight, S. D., Waksman, G. & Hultgren, S. J. (2000). Chaperone-assisted pilus assembly and bacterial attachment. Curr Opin Struct Biol 10, 548-56.</ref>. The paradigm is unique among TAD for his specificity toward GlcNAc. The binding site is located laterally and not at the tip of the pili, therefore the long and flexible F17 fimbriae could intrude between the microvilli of the epithelium, with the binding site of the lectin domain interacting laterally with GlcNAc-containing receptors. Five naturally occurring variants, differing in 1-18 amino acids of the adhesion domain have been identified<ref>De Kerpel, M., Van Molle, I., Brys, L., Wyns, L., De Greve, H. & Bouckaert, J. (2006). N-terminal truncation enables crystallization of the receptor-binding domain of the FedF bacterial adhesin. Acta Crystallogr Sect F Struct Biol Cryst Commun 62, 1278-82.</ref>.

== CFG Participating Investigators contributing to the understanding of this paradigm ==
This is an emerging field of investigation and contributions arose from a small number of CFG Participating Investigators (PIs). These include: Esther Bullit, Eric Cox, Anne Imberty, Remy Loris, James Nataro

== Progress toward understanding this GBP paradigm ==

=== Carbohydrate ligands ===

The F17G adhesin is most specific for the disaccharide GlcNAcb1,3Gal that can be recognised as a terminal or internal sequence in bovine glycophorin (<ref>Mouricout, M., Milhavet, M., Durié, C., Grange, P. Characterization of glycoprotein glycan receptors for Escherichia coli F17 fimbrial lectin, Microb. Pathog. (1995) 18, 297-306</ref>):
 
[[File:carbSynthe_0691_D000.jpg]]
 
The branched form gives a closely similar fluorescent signal:
 
[[File:carbSynthe_0897_D000.jpg]]
 
The presence of the b1,3 linkage of N-acetyl glucosamine to galactose enhances the affinity for F17G at least 2-fold, compared to the monosaccharide N-acetyl glucosamine, as validated using surface plasmon resonance measurements. Second best binders are the b1,4 and b1,6 galactose linked disaccharides, whereas chitobiose that is also a characterized inhibitor of F17G-mediated bacterial adhesion is clearly lagging behind. F17G can thus be ranked under glycan binding proteins that display high selectivity.

=== Cellular expression of GBP and ligands ===

F17G adhesins are constitutively expressed on enterotoxigenic E. coli infecting neonatal lambs, calves, and goat kids.

=== Biosynthesis of ligands ===
 
=== Structure ===

The F17G adhesin is a two-domain adhesin (TDA) located at the F17 fimbrial tip. The determination of the crystal structure of the F17G lectin domain led to the discovery of the variable immunoglobulin-like structure
as a paradigm for bacterial fimbrial TDAs <ref name=" Buts, L2003">
</ref>. F17G has a shallow groove for carbohydrate recognition on its flank.

 
[[File:F17G_Igfold.jpg]]
 

=== Biological roles of GBP-ligand interaction ===

The F17G fimbrial lectin enhances intestinal colonization in the early life of ruminants. The long and flexible F17 fimbriae can penetrate deep between intestinal microvilli, where the fimbrial tip adhesin finds its glycan receptors. The subsequent secretion of heat stable and heat lable toxins can lead to severe diarhea.

== CFG resources used in investigations ==
The best examples of CFG contributions to this paradigm are described below, with links to specific data sets. For a complete list of CFG data and resources relating to this paradigm, see the CFG database search results for [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=fimbriae&maxresults=20 fimbriae] and [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=pili&maxresults=20 pili].

=== Glycan profiling ===

 
=== Glycogene microarray ===

 
=== Knockout mouse lines ===

 
=== Glycan array ===
F17G adhesins have been screened for their glycan specificity (click [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_PA_v2_177_11182005 here]). To see all glycan array results for F17G adhesin, click [http://www.functionalglycomics.org/glycomics/search/jsp/result.jsp?query=F17G&cat=coreh here].

== Related GBPs ==
FedF, CfaE, FimH, PapG, CupB6

The specificity of some of the other fimbrial tip adhesins was determined by CFG glycan array analysis ([http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_2358 ''P. gingivalis'' fimbriae], [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_PA_v2_178_11182005 ''E. coli'' FedF adhesin], [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_1106 ''E. coli'' CfaE adhesin from CFA/I pili])

== References ==
<references/>

== Acknowledgements ==
The CFG is grateful to the following PIs for their contributions to this wiki page: Alisdair Boraston, Julie Bouckaert, Anne Imberty

F17G/GafD

2010-06-16T07:36:45Z

Julie Bouckaert: /* Structure */

The F17-G (GafD) adhesin at the tip of flexible F17 fimbriae of enterotoxigenic ''Escherichia coli'' mediates binding to N-acetyl-β-D-glucosamine-presenting receptors on the microvilli of the intestinal epithelium of ruminants, leading to diarrhea or septicaemia. F17-G belong to two-domain adhesins (TDA)s consisting of a pilin domain and a lectin domain, both having an Ig-fold joined via a short interdomain linker<ref>Buts, L., Bouckaert, J., De Gents, E., Loris, R., Oscarson, S., Lahmann, M., Messens, J., Brosens, E., Wyns, L. & De Greve, H. (2003). The fimbrial adhesin F17-G of enterotoxigenic Escherichia coli has an immunoglobulin-like lectin domain that binds N-acetylglucosamine. Mol. Microb. 49, 705-715.</ref><ref>Merckel, M. C., Tanskanen, J., Edelman, S., Westerlund-Wilkström, B., Korhonen, T. K. & Goldman, A. (2003). The structural basis of receptor-binding by Escherichia coli associaed with diarrhea and septicemia. J. Mol. Biol. 331, 897-905.</ref>. Related adhesins have been characterized in enteropathogenic ''E. coli'' ( FedF on F18 fimbriae<ref>Coddens, A., Diswall, M., Angstrom, J., Breimer, M. E., Goddeeris, B., Cox, E. & Teneberg, S. (2009). Recognition of blood group ABH type 1 determinants by the FedF adhesin of F18-fimbriated Escherichia coli. J Biol Chem 284, 9713-26.</ref> and CfaE on CFA/I pili<ref>Poole, S. T., McVeigh, A. L., Anantha, R. P., Lee, L. H., Akay, Y. M., Pontzer, E. A., Scott, D. A., Bullitt, E. & Savarino, S. J. (2007). Donor strand complementation governs intersubunit interaction of fimbriae of the alternate chaperone pathway. Mol Microbiol 63, 1372-84.</ref>) ) and uropathogenic ones (FimH on type 1 fimbriae<ref>Bouckaert, J., Berglund, J., Schembri, M., De Gents, E., Cools, L., Wuhrer, M., Hung, C.-S., Pinkner, J., Slättegard, R., Savialov, A., Choudhury, D., Langermann, S., Hultgren, S. J., Wyns, L., Klemm, P., Oscarson, S., Knight, S. D. & De Greve, H. (2005). Receptor binding studies disclose a novel class of high-affinity inhibitors of the Escherichia coli FimH adhesin. Mol. Microb. 55, 441-455.</ref> and PapG on P-pili<ref>Dodson, K. W., Pinkner, J. S., Rose, T., Magnusson, G., Hultgren, S. J. & Waksman, G. (2001). Structural basis of the interaction of the pyelonephritic E. coli adhesin to ist human kideny receptor. Cell 105, 733-743.</ref>). Fimbrial adhesins from other organisms, such as CupB6 from ''Pseudomonas aeruginosa'' are also investigated. All share the immunoglobulin-like fold of the two structural components, despite lack of any sequence identity and diversity in carbohydrate specificity and binding site, and the corresponding pili are assembled by the chaperone-usher pathway<ref>De Greve, H., Wyns, L. & Bouckaert, J. (2007). Combining sites of bacterial fimbriae. Curr Opin Struct Biol 17, 506-12.</ref><ref>Sauer, F. G., Barnhart, M., Choudhury, D., Knight, S. D., Waksman, G. & Hultgren, S. J. (2000). Chaperone-assisted pilus assembly and bacterial attachment. Curr Opin Struct Biol 10, 548-56.</ref>. The paradigm is unique among TAD for his specificity toward GlcNAc. The binding site is located laterally and not at the tip of the pili, therefore the long and flexible F17 fimbriae could intrude between the microvilli of the epithelium, with the binding site of the lectin domain interacting laterally with GlcNAc-containing receptors. Five naturally occurring variants, differing in 1-18 amino acids of the adhesion domain have been identified<ref>De Kerpel, M., Van Molle, I., Brys, L., Wyns, L., De Greve, H. & Bouckaert, J. (2006). N-terminal truncation enables crystallization of the receptor-binding domain of the FedF bacterial adhesin. Acta Crystallogr Sect F Struct Biol Cryst Commun 62, 1278-82.</ref>.

== CFG Participating Investigators contributing to the understanding of this paradigm ==
This is an emerging field of investigation and contributions arose from a small number of CFG Participating Investigators (PIs). These include: Esther Bullit, Eric Cox, Anne Imberty, Remy Loris, James Nataro

== Progress toward understanding this GBP paradigm ==

=== Carbohydrate ligands ===

The F17G adhesin is most specific for the disaccharide GlcNAcb1,3Gal that can be recognised as a terminal or internal sequence in bovine glycophorin (<ref>Mouricout, M., Milhavet, M., Durié, C., Grange, P. Characterization of glycoprotein glycan receptors for Escherichia coli F17 fimbrial lectin, Microb. Pathog. (1995) 18, 297-306</ref>):
 
[[File:carbSynthe_0691_D000.jpg]]
 

=== Cellular expression ===

F17G adhesins are constitutively expressed on enterotoxigenic E. coli infecting neonatal lambs, calfs and goat kids.

=== Structure ===

The F17G adhesin is a two-domain adhesin (TDA) located at the F17 fimbrial tip. The determination of the crystal structure of the F17G lectin domain led to the discovery of the variable immunoglobulin-like structure
as a paradigm for bacterial fimbrial TDAs <ref>1</ref>. F17G has a shallow groove for carbohydrate recognition on its flank.

 
[[File:F17G_Igfold.jpg]]
 

=== Biological roles of GBP-ligand interaction ===

The F17G fimbrial lectin enhances intestinal colonization in the early life of ruminants. The long and flexible F17 fimbriae can penetrate deep between intestinal microvilli, where the fimbrial tip adhesin finds its glycan receptors. The subsequent secretion of heat stable and heat lable toxins can lead to severe diarhea.

== CFG resources used in investigations ==
The best examples of CFG contributions to this paradigm are described below, with links to specific data sets. For a complete list of CFG data and resources relating to this paradigm, see the CFG database search results for [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=fimbriae&maxresults=20 fimbriae] and [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=pili&maxresults=20 pili].

=== Glycan profiling ===

 
=== Glycogene microarray ===

 
=== Knockout mouse lines ===

 
=== Glycan array ===
F17G adhesins have been screened for their glycan specificity: http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=F17G&maxresults=20

== Related GBPs ==
FedF, CfaE, FimH, PapG, CupB6

The specificity of some of the other fimbrial tip adhesins was determined by CFG glycan array analysis ([http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_2358 ''P. gingivalis'' fimbriae], [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_PA_v2_178_11182005 ''E. coli'' FedF adhesin], [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_1106 ''E. coli'' CfaE adhesin from CFA/I pili])

== References ==
<references/>

== Acknowledgements ==
The CFG is grateful to the following PIs for their contributions to this wiki page: Alisdair Boraston, Julie Bouckaert, Anne Imberty

F17G/GafD

2010-06-16T07:36:02Z

Julie Bouckaert: /* Biological roles of GBP-ligand interaction */

The F17-G (GafD) adhesin at the tip of flexible F17 fimbriae of enterotoxigenic ''Escherichia coli'' mediates binding to N-acetyl-β-D-glucosamine-presenting receptors on the microvilli of the intestinal epithelium of ruminants, leading to diarrhea or septicaemia. F17-G belong to two-domain adhesins (TDA)s consisting of a pilin domain and a lectin domain, both having an Ig-fold joined via a short interdomain linker<ref>Buts, L., Bouckaert, J., De Gents, E., Loris, R., Oscarson, S., Lahmann, M., Messens, J., Brosens, E., Wyns, L. & De Greve, H. (2003). The fimbrial adhesin F17-G of enterotoxigenic Escherichia coli has an immunoglobulin-like lectin domain that binds N-acetylglucosamine. Mol. Microb. 49, 705-715.</ref><ref>Merckel, M. C., Tanskanen, J., Edelman, S., Westerlund-Wilkström, B., Korhonen, T. K. & Goldman, A. (2003). The structural basis of receptor-binding by Escherichia coli associaed with diarrhea and septicemia. J. Mol. Biol. 331, 897-905.</ref>. Related adhesins have been characterized in enteropathogenic ''E. coli'' ( FedF on F18 fimbriae<ref>Coddens, A., Diswall, M., Angstrom, J., Breimer, M. E., Goddeeris, B., Cox, E. & Teneberg, S. (2009). Recognition of blood group ABH type 1 determinants by the FedF adhesin of F18-fimbriated Escherichia coli. J Biol Chem 284, 9713-26.</ref> and CfaE on CFA/I pili<ref>Poole, S. T., McVeigh, A. L., Anantha, R. P., Lee, L. H., Akay, Y. M., Pontzer, E. A., Scott, D. A., Bullitt, E. & Savarino, S. J. (2007). Donor strand complementation governs intersubunit interaction of fimbriae of the alternate chaperone pathway. Mol Microbiol 63, 1372-84.</ref>) ) and uropathogenic ones (FimH on type 1 fimbriae<ref>Bouckaert, J., Berglund, J., Schembri, M., De Gents, E., Cools, L., Wuhrer, M., Hung, C.-S., Pinkner, J., Slättegard, R., Savialov, A., Choudhury, D., Langermann, S., Hultgren, S. J., Wyns, L., Klemm, P., Oscarson, S., Knight, S. D. & De Greve, H. (2005). Receptor binding studies disclose a novel class of high-affinity inhibitors of the Escherichia coli FimH adhesin. Mol. Microb. 55, 441-455.</ref> and PapG on P-pili<ref>Dodson, K. W., Pinkner, J. S., Rose, T., Magnusson, G., Hultgren, S. J. & Waksman, G. (2001). Structural basis of the interaction of the pyelonephritic E. coli adhesin to ist human kideny receptor. Cell 105, 733-743.</ref>). Fimbrial adhesins from other organisms, such as CupB6 from ''Pseudomonas aeruginosa'' are also investigated. All share the immunoglobulin-like fold of the two structural components, despite lack of any sequence identity and diversity in carbohydrate specificity and binding site, and the corresponding pili are assembled by the chaperone-usher pathway<ref>De Greve, H., Wyns, L. & Bouckaert, J. (2007). Combining sites of bacterial fimbriae. Curr Opin Struct Biol 17, 506-12.</ref><ref>Sauer, F. G., Barnhart, M., Choudhury, D., Knight, S. D., Waksman, G. & Hultgren, S. J. (2000). Chaperone-assisted pilus assembly and bacterial attachment. Curr Opin Struct Biol 10, 548-56.</ref>. The paradigm is unique among TAD for his specificity toward GlcNAc. The binding site is located laterally and not at the tip of the pili, therefore the long and flexible F17 fimbriae could intrude between the microvilli of the epithelium, with the binding site of the lectin domain interacting laterally with GlcNAc-containing receptors. Five naturally occurring variants, differing in 1-18 amino acids of the adhesion domain have been identified<ref>De Kerpel, M., Van Molle, I., Brys, L., Wyns, L., De Greve, H. & Bouckaert, J. (2006). N-terminal truncation enables crystallization of the receptor-binding domain of the FedF bacterial adhesin. Acta Crystallogr Sect F Struct Biol Cryst Commun 62, 1278-82.</ref>.

== CFG Participating Investigators contributing to the understanding of this paradigm ==
This is an emerging field of investigation and contributions arose from a small number of CFG Participating Investigators (PIs). These include: Esther Bullit, Eric Cox, Anne Imberty, Remy Loris, James Nataro

== Progress toward understanding this GBP paradigm ==

=== Carbohydrate ligands ===

The F17G adhesin is most specific for the disaccharide GlcNAcb1,3Gal that can be recognised as a terminal or internal sequence in bovine glycophorin (<ref>Mouricout, M., Milhavet, M., Durié, C., Grange, P. Characterization of glycoprotein glycan receptors for Escherichia coli F17 fimbrial lectin, Microb. Pathog. (1995) 18, 297-306</ref>):
 
[[File:carbSynthe_0691_D000.jpg]]
 

=== Cellular expression ===

F17G adhesins are constitutively expressed on enterotoxigenic E. coli infecting neonatal lambs, calfs and goat kids.

=== Structure ===

The F17G adhesin is a two-domain adhesin (TDA) located at the F17 fimbrial tip. The determination of the crystal structure of the F17G lectin domain led to the discovery of the variable immunoglobulin-like structure
as a paradigm for bacterial fimbrial TDAs. F17G has a shallow groove for carbohydrate recognition on its flank.

 
[[File:F17G_Igfold.jpg]]
 

=== Biological roles of GBP-ligand interaction ===

The F17G fimbrial lectin enhances intestinal colonization in the early life of ruminants. The long and flexible F17 fimbriae can penetrate deep between intestinal microvilli, where the fimbrial tip adhesin finds its glycan receptors. The subsequent secretion of heat stable and heat lable toxins can lead to severe diarhea.

== CFG resources used in investigations ==
The best examples of CFG contributions to this paradigm are described below, with links to specific data sets. For a complete list of CFG data and resources relating to this paradigm, see the CFG database search results for [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=fimbriae&maxresults=20 fimbriae] and [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=pili&maxresults=20 pili].

=== Glycan profiling ===

 
=== Glycogene microarray ===

 
=== Knockout mouse lines ===

 
=== Glycan array ===
F17G adhesins have been screened for their glycan specificity: http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=F17G&maxresults=20

== Related GBPs ==
FedF, CfaE, FimH, PapG, CupB6

The specificity of some of the other fimbrial tip adhesins was determined by CFG glycan array analysis ([http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_2358 ''P. gingivalis'' fimbriae], [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_PA_v2_178_11182005 ''E. coli'' FedF adhesin], [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_1106 ''E. coli'' CfaE adhesin from CFA/I pili])

== References ==
<references/>

== Acknowledgements ==
The CFG is grateful to the following PIs for their contributions to this wiki page: Alisdair Boraston, Julie Bouckaert, Anne Imberty

F17G/GafD

2010-06-16T07:30:45Z

Julie Bouckaert: /* Related GBPs */

The F17-G (GafD) adhesin at the tip of flexible F17 fimbriae of enterotoxigenic ''Escherichia coli'' mediates binding to N-acetyl-β-D-glucosamine-presenting receptors on the microvilli of the intestinal epithelium of ruminants, leading to diarrhea or septicaemia. F17-G belong to two-domain adhesins (TDA)s consisting of a pilin domain and a lectin domain, both having an Ig-fold joined via a short interdomain linker<ref>Buts, L., Bouckaert, J., De Gents, E., Loris, R., Oscarson, S., Lahmann, M., Messens, J., Brosens, E., Wyns, L. & De Greve, H. (2003). The fimbrial adhesin F17-G of enterotoxigenic Escherichia coli has an immunoglobulin-like lectin domain that binds N-acetylglucosamine. Mol. Microb. 49, 705-715.</ref><ref>Merckel, M. C., Tanskanen, J., Edelman, S., Westerlund-Wilkström, B., Korhonen, T. K. & Goldman, A. (2003). The structural basis of receptor-binding by Escherichia coli associaed with diarrhea and septicemia. J. Mol. Biol. 331, 897-905.</ref>. Related adhesins have been characterized in enteropathogenic ''E. coli'' ( FedF on F18 fimbriae<ref>Coddens, A., Diswall, M., Angstrom, J., Breimer, M. E., Goddeeris, B., Cox, E. & Teneberg, S. (2009). Recognition of blood group ABH type 1 determinants by the FedF adhesin of F18-fimbriated Escherichia coli. J Biol Chem 284, 9713-26.</ref> and CfaE on CFA/I pili<ref>Poole, S. T., McVeigh, A. L., Anantha, R. P., Lee, L. H., Akay, Y. M., Pontzer, E. A., Scott, D. A., Bullitt, E. & Savarino, S. J. (2007). Donor strand complementation governs intersubunit interaction of fimbriae of the alternate chaperone pathway. Mol Microbiol 63, 1372-84.</ref>) ) and uropathogenic ones (FimH on type 1 fimbriae<ref>Bouckaert, J., Berglund, J., Schembri, M., De Gents, E., Cools, L., Wuhrer, M., Hung, C.-S., Pinkner, J., Slättegard, R., Savialov, A., Choudhury, D., Langermann, S., Hultgren, S. J., Wyns, L., Klemm, P., Oscarson, S., Knight, S. D. & De Greve, H. (2005). Receptor binding studies disclose a novel class of high-affinity inhibitors of the Escherichia coli FimH adhesin. Mol. Microb. 55, 441-455.</ref> and PapG on P-pili<ref>Dodson, K. W., Pinkner, J. S., Rose, T., Magnusson, G., Hultgren, S. J. & Waksman, G. (2001). Structural basis of the interaction of the pyelonephritic E. coli adhesin to ist human kideny receptor. Cell 105, 733-743.</ref>). Fimbrial adhesins from other organisms, such as CupB6 from ''Pseudomonas aeruginosa'' are also investigated. All share the immunoglobulin-like fold of the two structural components, despite lack of any sequence identity and diversity in carbohydrate specificity and binding site, and the corresponding pili are assembled by the chaperone-usher pathway<ref>De Greve, H., Wyns, L. & Bouckaert, J. (2007). Combining sites of bacterial fimbriae. Curr Opin Struct Biol 17, 506-12.</ref><ref>Sauer, F. G., Barnhart, M., Choudhury, D., Knight, S. D., Waksman, G. & Hultgren, S. J. (2000). Chaperone-assisted pilus assembly and bacterial attachment. Curr Opin Struct Biol 10, 548-56.</ref>. The paradigm is unique among TAD for his specificity toward GlcNAc. The binding site is located laterally and not at the tip of the pili, therefore the long and flexible F17 fimbriae could intrude between the microvilli of the epithelium, with the binding site of the lectin domain interacting laterally with GlcNAc-containing receptors. Five naturally occurring variants, differing in 1-18 amino acids of the adhesion domain have been identified<ref>De Kerpel, M., Van Molle, I., Brys, L., Wyns, L., De Greve, H. & Bouckaert, J. (2006). N-terminal truncation enables crystallization of the receptor-binding domain of the FedF bacterial adhesin. Acta Crystallogr Sect F Struct Biol Cryst Commun 62, 1278-82.</ref>.

== CFG Participating Investigators contributing to the understanding of this paradigm ==
This is an emerging field of investigation and contributions arose from a small number of CFG Participating Investigators (PIs). These include: Esther Bullit, Eric Cox, Anne Imberty, Remy Loris, James Nataro

== Progress toward understanding this GBP paradigm ==

=== Carbohydrate ligands ===

The F17G adhesin is most specific for the disaccharide GlcNAcb1,3Gal that can be recognised as a terminal or internal sequence in bovine glycophorin (<ref>Mouricout, M., Milhavet, M., Durié, C., Grange, P. Characterization of glycoprotein glycan receptors for Escherichia coli F17 fimbrial lectin, Microb. Pathog. (1995) 18, 297-306</ref>):
 
[[File:carbSynthe_0691_D000.jpg]]
 

=== Cellular expression ===

F17G adhesins are constitutively expressed on enterotoxigenic E. coli infecting neonatal lambs, calfs and goat kids.

=== Structure ===

The F17G adhesin is a two-domain adhesin (TDA) located at the F17 fimbrial tip. The determination of the crystal structure of the F17G lectin domain led to the discovery of the variable immunoglobulin-like structure
as a paradigm for bacterial fimbrial TDAs. F17G has a shallow groove for carbohydrate recognition on its flank.

 
[[File:F17G_Igfold.jpg]]
 

=== Biological roles of GBP-ligand interaction ===

 
== CFG resources used in investigations ==
The best examples of CFG contributions to this paradigm are described below, with links to specific data sets. For a complete list of CFG data and resources relating to this paradigm, see the CFG database search results for [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=fimbriae&maxresults=20 fimbriae] and [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=pili&maxresults=20 pili].

=== Glycan profiling ===

 
=== Glycogene microarray ===

 
=== Knockout mouse lines ===

 
=== Glycan array ===
F17G adhesins have been screened for their glycan specificity: http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=F17G&maxresults=20

== Related GBPs ==
FedF, CfaE, FimH, PapG, CupB6

The specificity of some of the other fimbrial tip adhesins was determined by CFG glycan array analysis ([http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_2358 ''P. gingivalis'' fimbriae], [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_PA_v2_178_11182005 ''E. coli'' FedF adhesin], [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_1106 ''E. coli'' CfaE adhesin from CFA/I pili])

== References ==
<references/>

== Acknowledgements ==
The CFG is grateful to the following PIs for their contributions to this wiki page: Alisdair Boraston, Julie Bouckaert, Anne Imberty

F17G/GafD

2010-06-16T07:30:23Z

Julie Bouckaert: /* Glycan array */

F17G/GafD

2010-06-15T05:50:33Z

Julie Bouckaert: /* Structure */

The F17-G (GafD) adhesin at the tip of flexible F17 fimbriae of enterotoxigenic ''Escherichia coli'' mediates binding to N-acetyl-β-D-glucosamine-presenting receptors on the microvilli of the intestinal epithelium of ruminants, leading to diarrhea or septicaemia. F17-G belong to two-domain adhesins (TDA)s consisting of a pilin domain and a lectin domain, both having an Ig-fold joined via a short interdomain linker<ref>Buts, L., Bouckaert, J., De Gents, E., Loris, R., Oscarson, S., Lahmann, M., Messens, J., Brosens, E., Wyns, L. & De Greve, H. (2003). The fimbrial adhesin F17-G of enterotoxigenic Escherichia coli has an immunoglobulin-like lectin domain that binds N-acetylglucosamine. Mol. Microb. 49, 705-715.</ref><ref>Merckel, M. C., Tanskanen, J., Edelman, S., Westerlund-Wilkström, B., Korhonen, T. K. & Goldman, A. (2003). The structural basis of receptor-binding by Escherichia coli associaed with diarrhea and septicemia. J. Mol. Biol. 331, 897-905.</ref>. Related adhesins have been characterized in enteropathogenic ''E. coli'' ( FedF on F18 fimbriae<ref>Coddens, A., Diswall, M., Angstrom, J., Breimer, M. E., Goddeeris, B., Cox, E. & Teneberg, S. (2009). Recognition of blood group ABH type 1 determinants by the FedF adhesin of F18-fimbriated Escherichia coli. J Biol Chem 284, 9713-26.</ref> and CfaE on CFA/I pili<ref>Poole, S. T., McVeigh, A. L., Anantha, R. P., Lee, L. H., Akay, Y. M., Pontzer, E. A., Scott, D. A., Bullitt, E. & Savarino, S. J. (2007). Donor strand complementation governs intersubunit interaction of fimbriae of the alternate chaperone pathway. Mol Microbiol 63, 1372-84.</ref>) ) and uropathogenic ones (FimH on type 1 fimbriae<ref>Bouckaert, J., Berglund, J., Schembri, M., De Gents, E., Cools, L., Wuhrer, M., Hung, C.-S., Pinkner, J., Slättegard, R., Savialov, A., Choudhury, D., Langermann, S., Hultgren, S. J., Wyns, L., Klemm, P., Oscarson, S., Knight, S. D. & De Greve, H. (2005). Receptor binding studies disclose a novel class of high-affinity inhibitors of the Escherichia coli FimH adhesin. Mol. Microb. 55, 441-455.</ref> and PapG on P-pili<ref>Dodson, K. W., Pinkner, J. S., Rose, T., Magnusson, G., Hultgren, S. J. & Waksman, G. (2001). Structural basis of the interaction of the pyelonephritic E. coli adhesin to ist human kideny receptor. Cell 105, 733-743.</ref>). Fimbrial adhesins from other organisms, such as CupB6 from ''Pseudomonas aeruginosa'' are also investigated. All share the immunoglobulin-like fold of the two structural components, despite lack of any sequence identity and diversity in carbohydrate specificity and binding site, and the corresponding pili are assembled by the chaperone-usher pathway<ref>De Greve, H., Wyns, L. & Bouckaert, J. (2007). Combining sites of bacterial fimbriae. Curr Opin Struct Biol 17, 506-12.</ref><ref>Sauer, F. G., Barnhart, M., Choudhury, D., Knight, S. D., Waksman, G. & Hultgren, S. J. (2000). Chaperone-assisted pilus assembly and bacterial attachment. Curr Opin Struct Biol 10, 548-56.</ref>. The paradigm is unique among TAD for his specificity toward GlcNAc. The binding site is located laterally and not at the tip of the pili, therefore the long and flexible F17 fimbriae could intrude between the microvilli of the epithelium, with the binding site of the lectin domain interacting laterally with GlcNAc-containing receptors. Five naturally occurring variants, differing in 1-18 amino acids of the adhesion domain have been identified<ref>De Kerpel, M., Van Molle, I., Brys, L., Wyns, L., De Greve, H. & Bouckaert, J. (2006). N-terminal truncation enables crystallization of the receptor-binding domain of the FedF bacterial adhesin. Acta Crystallogr Sect F Struct Biol Cryst Commun 62, 1278-82.</ref>.

== CFG Participating Investigators contributing to the understanding of this paradigm ==
This is an emerging field of investigation and contributions arose from a small number of CFG Participating Investigators (PIs). These include: Esther Bullit, Eric Cox, Anne Imberty, Remy Loris, James Nataro

== Progress toward understanding this GBP paradigm ==

=== Carbohydrate ligands ===

The F17G adhesin is most specific for the disaccharide GlcNAcb1,3Gal that can be recognised as a terminal or internal sequence in bovine glycophorin (<ref>Mouricout, M., Milhavet, M., Durié, C., Grange, P. Characterization of glycoprotein glycan receptors for Escherichia coli F17 fimbrial lectin, Microb. Pathog. (1995) 18, 297-306</ref>):

(carbSynthe_0691_D000.jpg)

=== Cellular expression ===

F17G adhesins are constitutively expressed on enterotoxigenic E. coli infecting neonatal lambs, calfs and goat kids.

=== Structure ===

The F17G adhesin is a two-domain adhesin (TDA) located at the F17 fimbrial tip. The determination of the crystal structure of the F17G lectin domain led to the discovery of the variable immunoglobulin-like structure
as a paradigm for bacterial fimbrial TDAs. F17G has a shallow groove for carbohydrate recognition on its flank.

(F17G figure and comparison)

=== Biological roles of GBP-ligand interaction ===

 
== CFG resources used in investigations ==
The best examples of CFG contributions to this paradigm are described below, with links to specific data sets. For a complete list of CFG data and resources relating to this paradigm, see the CFG database search results for [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=fimbriae&maxresults=20 fimbriae] and [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=pili&maxresults=20 pili].

=== Glycan profiling ===

 
=== Glycogene microarray ===

 
=== Knockout mouse lines ===

 
=== Glycan array ===
F17G adhesins have been screened for their glycan specificity: http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=F17G&maxresults=20

The specificity of some of the other fimbrial tip adhesins was determined by CFG glycan array analysis ([http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_2358 ''P. gingivalis'' fimbriae], [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_PA_v2_178_11182005 ''E. coli'' FedF adhesin], [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_1106 ''E. coli'' CfaE adhesin from CFA/I pili])

== Related GBPs ==
FedF, CfaE, FimH, PapG, CupB6

== References ==
<references/>

== Acknowledgements ==
The CFG is grateful to the following PIs for their contributions to this wiki page: Alisdair Boraston, Julie Bouckaert, Anne Imberty

F17G/GafD

2010-06-15T05:42:49Z

Julie Bouckaert: /* Structure */

The F17-G (GafD) adhesin at the tip of flexible F17 fimbriae of enterotoxigenic ''Escherichia coli'' mediates binding to N-acetyl-β-D-glucosamine-presenting receptors on the microvilli of the intestinal epithelium of ruminants, leading to diarrhea or septicaemia. F17-G belong to two-domain adhesins (TDA)s consisting of a pilin domain and a lectin domain, both having an Ig-fold joined via a short interdomain linker<ref>Buts, L., Bouckaert, J., De Gents, E., Loris, R., Oscarson, S., Lahmann, M., Messens, J., Brosens, E., Wyns, L. & De Greve, H. (2003). The fimbrial adhesin F17-G of enterotoxigenic Escherichia coli has an immunoglobulin-like lectin domain that binds N-acetylglucosamine. Mol. Microb. 49, 705-715.</ref><ref>Merckel, M. C., Tanskanen, J., Edelman, S., Westerlund-Wilkström, B., Korhonen, T. K. & Goldman, A. (2003). The structural basis of receptor-binding by Escherichia coli associaed with diarrhea and septicemia. J. Mol. Biol. 331, 897-905.</ref>. Related adhesins have been characterized in enteropathogenic ''E. coli'' ( FedF on F18 fimbriae<ref>Coddens, A., Diswall, M., Angstrom, J., Breimer, M. E., Goddeeris, B., Cox, E. & Teneberg, S. (2009). Recognition of blood group ABH type 1 determinants by the FedF adhesin of F18-fimbriated Escherichia coli. J Biol Chem 284, 9713-26.</ref> and CfaE on CFA/I pili<ref>Poole, S. T., McVeigh, A. L., Anantha, R. P., Lee, L. H., Akay, Y. M., Pontzer, E. A., Scott, D. A., Bullitt, E. & Savarino, S. J. (2007). Donor strand complementation governs intersubunit interaction of fimbriae of the alternate chaperone pathway. Mol Microbiol 63, 1372-84.</ref>) ) and uropathogenic ones (FimH on type 1 fimbriae<ref>Bouckaert, J., Berglund, J., Schembri, M., De Gents, E., Cools, L., Wuhrer, M., Hung, C.-S., Pinkner, J., Slättegard, R., Savialov, A., Choudhury, D., Langermann, S., Hultgren, S. J., Wyns, L., Klemm, P., Oscarson, S., Knight, S. D. & De Greve, H. (2005). Receptor binding studies disclose a novel class of high-affinity inhibitors of the Escherichia coli FimH adhesin. Mol. Microb. 55, 441-455.</ref> and PapG on P-pili<ref>Dodson, K. W., Pinkner, J. S., Rose, T., Magnusson, G., Hultgren, S. J. & Waksman, G. (2001). Structural basis of the interaction of the pyelonephritic E. coli adhesin to ist human kideny receptor. Cell 105, 733-743.</ref>). Fimbrial adhesins from other organisms, such as CupB6 from ''Pseudomonas aeruginosa'' are also investigated. All share the immunoglobulin-like fold of the two structural components, despite lack of any sequence identity and diversity in carbohydrate specificity and binding site, and the corresponding pili are assembled by the chaperone-usher pathway<ref>De Greve, H., Wyns, L. & Bouckaert, J. (2007). Combining sites of bacterial fimbriae. Curr Opin Struct Biol 17, 506-12.</ref><ref>Sauer, F. G., Barnhart, M., Choudhury, D., Knight, S. D., Waksman, G. & Hultgren, S. J. (2000). Chaperone-assisted pilus assembly and bacterial attachment. Curr Opin Struct Biol 10, 548-56.</ref>. The paradigm is unique among TAD for his specificity toward GlcNAc. The binding site is located laterally and not at the tip of the pili, therefore the long and flexible F17 fimbriae could intrude between the microvilli of the epithelium, with the binding site of the lectin domain interacting laterally with GlcNAc-containing receptors. Five naturally occurring variants, differing in 1-18 amino acids of the adhesion domain have been identified<ref>De Kerpel, M., Van Molle, I., Brys, L., Wyns, L., De Greve, H. & Bouckaert, J. (2006). N-terminal truncation enables crystallization of the receptor-binding domain of the FedF bacterial adhesin. Acta Crystallogr Sect F Struct Biol Cryst Commun 62, 1278-82.</ref>.

== CFG Participating Investigators contributing to the understanding of this paradigm ==
This is an emerging field of investigation and contributions arose from a small number of CFG Participating Investigators (PIs). These include: Esther Bullit, Eric Cox, Anne Imberty, Remy Loris, James Nataro

== Progress toward understanding this GBP paradigm ==

=== Carbohydrate ligands ===

The F17G adhesin is most specific for the disaccharide GlcNAcb1,3Gal that can be recognised as a terminal or internal sequence in bovine glycophorin (<ref>Mouricout, M., Milhavet, M., Durié, C., Grange, P. Characterization of glycoprotein glycan receptors for Escherichia coli F17 fimbrial lectin, Microb. Pathog. (1995) 18, 297-306</ref>):

(carbSynthe_0691_D000.jpg)

=== Cellular expression ===

F17G adhesins are constitutively expressed on enterotoxigenic E. coli infecting neonatal lambs, calfs and goat kids.

=== Structure ===

The F17G adhesin is a two-domain adhesin (TDA) located at the F17 fimbrial tip. The determination of the crystal structure of the F17G lectin domain led to the discovery of the variable immunoglobulin-like structure
as a a paradigm for bacterial fimbrial adhesins. F17G has a shallow groove for carbohydrate recognition at its flank.

(F17G figure and comparison)

=== Biological roles of GBP-ligand interaction ===

 
== CFG resources used in investigations ==
The best examples of CFG contributions to this paradigm are described below, with links to specific data sets. For a complete list of CFG data and resources relating to this paradigm, see the CFG database search results for [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=fimbriae&maxresults=20 fimbriae] and [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=pili&maxresults=20 pili].

=== Glycan profiling ===

 
=== Glycogene microarray ===

 
=== Knockout mouse lines ===

 
=== Glycan array ===
F17G adhesins have been screened for their glycan specificity: http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=F17G&maxresults=20

The specificity of some of the other fimbrial tip adhesins was determined by CFG glycan array analysis ([http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_2358 ''P. gingivalis'' fimbriae], [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_PA_v2_178_11182005 ''E. coli'' FedF adhesin], [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_1106 ''E. coli'' CfaE adhesin from CFA/I pili])

== Related GBPs ==
FedF, CfaE, FimH, PapG, CupB6

== References ==
<references/>

== Acknowledgements ==
The CFG is grateful to the following PIs for their contributions to this wiki page: Alisdair Boraston, Julie Bouckaert, Anne Imberty

F17G/GafD

2010-06-15T05:35:13Z

Julie Bouckaert: /* Cellular expression */

The F17-G (GafD) adhesin at the tip of flexible F17 fimbriae of enterotoxigenic ''Escherichia coli'' mediates binding to N-acetyl-β-D-glucosamine-presenting receptors on the microvilli of the intestinal epithelium of ruminants, leading to diarrhea or septicaemia. F17-G belong to two-domain adhesins (TDA)s consisting of a pilin domain and a lectin domain, both having an Ig-fold joined via a short interdomain linker<ref>Buts, L., Bouckaert, J., De Gents, E., Loris, R., Oscarson, S., Lahmann, M., Messens, J., Brosens, E., Wyns, L. & De Greve, H. (2003). The fimbrial adhesin F17-G of enterotoxigenic Escherichia coli has an immunoglobulin-like lectin domain that binds N-acetylglucosamine. Mol. Microb. 49, 705-715.</ref><ref>Merckel, M. C., Tanskanen, J., Edelman, S., Westerlund-Wilkström, B., Korhonen, T. K. & Goldman, A. (2003). The structural basis of receptor-binding by Escherichia coli associaed with diarrhea and septicemia. J. Mol. Biol. 331, 897-905.</ref>. Related adhesins have been characterized in enteropathogenic ''E. coli'' ( FedF on F18 fimbriae<ref>Coddens, A., Diswall, M., Angstrom, J., Breimer, M. E., Goddeeris, B., Cox, E. & Teneberg, S. (2009). Recognition of blood group ABH type 1 determinants by the FedF adhesin of F18-fimbriated Escherichia coli. J Biol Chem 284, 9713-26.</ref> and CfaE on CFA/I pili<ref>Poole, S. T., McVeigh, A. L., Anantha, R. P., Lee, L. H., Akay, Y. M., Pontzer, E. A., Scott, D. A., Bullitt, E. & Savarino, S. J. (2007). Donor strand complementation governs intersubunit interaction of fimbriae of the alternate chaperone pathway. Mol Microbiol 63, 1372-84.</ref>) ) and uropathogenic ones (FimH on type 1 fimbriae<ref>Bouckaert, J., Berglund, J., Schembri, M., De Gents, E., Cools, L., Wuhrer, M., Hung, C.-S., Pinkner, J., Slättegard, R., Savialov, A., Choudhury, D., Langermann, S., Hultgren, S. J., Wyns, L., Klemm, P., Oscarson, S., Knight, S. D. & De Greve, H. (2005). Receptor binding studies disclose a novel class of high-affinity inhibitors of the Escherichia coli FimH adhesin. Mol. Microb. 55, 441-455.</ref> and PapG on P-pili<ref>Dodson, K. W., Pinkner, J. S., Rose, T., Magnusson, G., Hultgren, S. J. & Waksman, G. (2001). Structural basis of the interaction of the pyelonephritic E. coli adhesin to ist human kideny receptor. Cell 105, 733-743.</ref>). Fimbrial adhesins from other organisms, such as CupB6 from ''Pseudomonas aeruginosa'' are also investigated. All share the immunoglobulin-like fold of the two structural components, despite lack of any sequence identity and diversity in carbohydrate specificity and binding site, and the corresponding pili are assembled by the chaperone-usher pathway<ref>De Greve, H., Wyns, L. & Bouckaert, J. (2007). Combining sites of bacterial fimbriae. Curr Opin Struct Biol 17, 506-12.</ref><ref>Sauer, F. G., Barnhart, M., Choudhury, D., Knight, S. D., Waksman, G. & Hultgren, S. J. (2000). Chaperone-assisted pilus assembly and bacterial attachment. Curr Opin Struct Biol 10, 548-56.</ref>. The paradigm is unique among TAD for his specificity toward GlcNAc. The binding site is located laterally and not at the tip of the pili, therefore the long and flexible F17 fimbriae could intrude between the microvilli of the epithelium, with the binding site of the lectin domain interacting laterally with GlcNAc-containing receptors. Five naturally occurring variants, differing in 1-18 amino acids of the adhesion domain have been identified<ref>De Kerpel, M., Van Molle, I., Brys, L., Wyns, L., De Greve, H. & Bouckaert, J. (2006). N-terminal truncation enables crystallization of the receptor-binding domain of the FedF bacterial adhesin. Acta Crystallogr Sect F Struct Biol Cryst Commun 62, 1278-82.</ref>.

== CFG Participating Investigators contributing to the understanding of this paradigm ==
This is an emerging field of investigation and contributions arose from a small number of CFG Participating Investigators (PIs). These include: Esther Bullit, Eric Cox, Anne Imberty, Remy Loris, James Nataro

== Progress toward understanding this GBP paradigm ==

=== Carbohydrate ligands ===

The F17G adhesin is most specific for the disaccharide GlcNAcb1,3Gal that can be recognised as a terminal or internal sequence in bovine glycophorin (<ref>Mouricout, M., Milhavet, M., Durié, C., Grange, P. Characterization of glycoprotein glycan receptors for Escherichia coli F17 fimbrial lectin, Microb. Pathog. (1995) 18, 297-306</ref>):

(carbSynthe_0691_D000.jpg)

=== Cellular expression ===

F17G adhesins are constitutively expressed on enterotoxigenic E. coli infecting neonatal lambs, calfs and goat kids.

=== Structure ===

< >

=== Biological roles of GBP-ligand interaction ===

 
== CFG resources used in investigations ==
The best examples of CFG contributions to this paradigm are described below, with links to specific data sets. For a complete list of CFG data and resources relating to this paradigm, see the CFG database search results for [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=fimbriae&maxresults=20 fimbriae] and [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=pili&maxresults=20 pili].

=== Glycan profiling ===

 
=== Glycogene microarray ===

 
=== Knockout mouse lines ===

 
=== Glycan array ===
F17G adhesins have been screened for their glycan specificity: http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=F17G&maxresults=20

The specificity of some of the other fimbrial tip adhesins was determined by CFG glycan array analysis ([http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_2358 ''P. gingivalis'' fimbriae], [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_PA_v2_178_11182005 ''E. coli'' FedF adhesin], [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_1106 ''E. coli'' CfaE adhesin from CFA/I pili])

== Related GBPs ==
FedF, CfaE, FimH, PapG, CupB6

== References ==
<references/>

== Acknowledgements ==
The CFG is grateful to the following PIs for their contributions to this wiki page: Alisdair Boraston, Julie Bouckaert, Anne Imberty

F17G/GafD

2010-06-15T05:35:01Z

Julie Bouckaert: /* Carbohydrate ligands */

The F17-G (GafD) adhesin at the tip of flexible F17 fimbriae of enterotoxigenic ''Escherichia coli'' mediates binding to N-acetyl-β-D-glucosamine-presenting receptors on the microvilli of the intestinal epithelium of ruminants, leading to diarrhea or septicaemia. F17-G belong to two-domain adhesins (TDA)s consisting of a pilin domain and a lectin domain, both having an Ig-fold joined via a short interdomain linker<ref>Buts, L., Bouckaert, J., De Gents, E., Loris, R., Oscarson, S., Lahmann, M., Messens, J., Brosens, E., Wyns, L. & De Greve, H. (2003). The fimbrial adhesin F17-G of enterotoxigenic Escherichia coli has an immunoglobulin-like lectin domain that binds N-acetylglucosamine. Mol. Microb. 49, 705-715.</ref><ref>Merckel, M. C., Tanskanen, J., Edelman, S., Westerlund-Wilkström, B., Korhonen, T. K. & Goldman, A. (2003). The structural basis of receptor-binding by Escherichia coli associaed with diarrhea and septicemia. J. Mol. Biol. 331, 897-905.</ref>. Related adhesins have been characterized in enteropathogenic ''E. coli'' ( FedF on F18 fimbriae<ref>Coddens, A., Diswall, M., Angstrom, J., Breimer, M. E., Goddeeris, B., Cox, E. & Teneberg, S. (2009). Recognition of blood group ABH type 1 determinants by the FedF adhesin of F18-fimbriated Escherichia coli. J Biol Chem 284, 9713-26.</ref> and CfaE on CFA/I pili<ref>Poole, S. T., McVeigh, A. L., Anantha, R. P., Lee, L. H., Akay, Y. M., Pontzer, E. A., Scott, D. A., Bullitt, E. & Savarino, S. J. (2007). Donor strand complementation governs intersubunit interaction of fimbriae of the alternate chaperone pathway. Mol Microbiol 63, 1372-84.</ref>) ) and uropathogenic ones (FimH on type 1 fimbriae<ref>Bouckaert, J., Berglund, J., Schembri, M., De Gents, E., Cools, L., Wuhrer, M., Hung, C.-S., Pinkner, J., Slättegard, R., Savialov, A., Choudhury, D., Langermann, S., Hultgren, S. J., Wyns, L., Klemm, P., Oscarson, S., Knight, S. D. & De Greve, H. (2005). Receptor binding studies disclose a novel class of high-affinity inhibitors of the Escherichia coli FimH adhesin. Mol. Microb. 55, 441-455.</ref> and PapG on P-pili<ref>Dodson, K. W., Pinkner, J. S., Rose, T., Magnusson, G., Hultgren, S. J. & Waksman, G. (2001). Structural basis of the interaction of the pyelonephritic E. coli adhesin to ist human kideny receptor. Cell 105, 733-743.</ref>). Fimbrial adhesins from other organisms, such as CupB6 from ''Pseudomonas aeruginosa'' are also investigated. All share the immunoglobulin-like fold of the two structural components, despite lack of any sequence identity and diversity in carbohydrate specificity and binding site, and the corresponding pili are assembled by the chaperone-usher pathway<ref>De Greve, H., Wyns, L. & Bouckaert, J. (2007). Combining sites of bacterial fimbriae. Curr Opin Struct Biol 17, 506-12.</ref><ref>Sauer, F. G., Barnhart, M., Choudhury, D., Knight, S. D., Waksman, G. & Hultgren, S. J. (2000). Chaperone-assisted pilus assembly and bacterial attachment. Curr Opin Struct Biol 10, 548-56.</ref>. The paradigm is unique among TAD for his specificity toward GlcNAc. The binding site is located laterally and not at the tip of the pili, therefore the long and flexible F17 fimbriae could intrude between the microvilli of the epithelium, with the binding site of the lectin domain interacting laterally with GlcNAc-containing receptors. Five naturally occurring variants, differing in 1-18 amino acids of the adhesion domain have been identified<ref>De Kerpel, M., Van Molle, I., Brys, L., Wyns, L., De Greve, H. & Bouckaert, J. (2006). N-terminal truncation enables crystallization of the receptor-binding domain of the FedF bacterial adhesin. Acta Crystallogr Sect F Struct Biol Cryst Commun 62, 1278-82.</ref>.

== CFG Participating Investigators contributing to the understanding of this paradigm ==
This is an emerging field of investigation and contributions arose from a small number of CFG Participating Investigators (PIs). These include: Esther Bullit, Eric Cox, Anne Imberty, Remy Loris, James Nataro

== Progress toward understanding this GBP paradigm ==

=== Carbohydrate ligands ===

The F17G adhesin is most specific for the disaccharide GlcNAcb1,3Gal that can be recognised as a terminal or internal sequence in bovine glycophorin (<ref>Mouricout, M., Milhavet, M., Durié, C., Grange, P. Characterization of glycoprotein glycan receptors for Escherichia coli F17 fimbrial lectin, Microb. Pathog. (1995) 18, 297-306</ref>):

(carbSynthe_0691_D000.jpg)

=== Cellular expression ===

<F17G adhesins are constitutively expressed on enterotoxigenic E. coli infecting neonatal lambs, calfs and goat kids.>

=== Structure ===

< >

=== Biological roles of GBP-ligand interaction ===

 
== CFG resources used in investigations ==
The best examples of CFG contributions to this paradigm are described below, with links to specific data sets. For a complete list of CFG data and resources relating to this paradigm, see the CFG database search results for [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=fimbriae&maxresults=20 fimbriae] and [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=pili&maxresults=20 pili].

=== Glycan profiling ===

 
=== Glycogene microarray ===

 
=== Knockout mouse lines ===

 
=== Glycan array ===
F17G adhesins have been screened for their glycan specificity: http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=F17G&maxresults=20

The specificity of some of the other fimbrial tip adhesins was determined by CFG glycan array analysis ([http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_2358 ''P. gingivalis'' fimbriae], [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_PA_v2_178_11182005 ''E. coli'' FedF adhesin], [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_1106 ''E. coli'' CfaE adhesin from CFA/I pili])

== Related GBPs ==
FedF, CfaE, FimH, PapG, CupB6

== References ==
<references/>

== Acknowledgements ==
The CFG is grateful to the following PIs for their contributions to this wiki page: Alisdair Boraston, Julie Bouckaert, Anne Imberty

F17G/GafD

2010-06-15T05:34:34Z

Julie Bouckaert: /* Carbohydrate ligands */

The F17-G (GafD) adhesin at the tip of flexible F17 fimbriae of enterotoxigenic ''Escherichia coli'' mediates binding to N-acetyl-β-D-glucosamine-presenting receptors on the microvilli of the intestinal epithelium of ruminants, leading to diarrhea or septicaemia. F17-G belong to two-domain adhesins (TDA)s consisting of a pilin domain and a lectin domain, both having an Ig-fold joined via a short interdomain linker<ref>Buts, L., Bouckaert, J., De Gents, E., Loris, R., Oscarson, S., Lahmann, M., Messens, J., Brosens, E., Wyns, L. & De Greve, H. (2003). The fimbrial adhesin F17-G of enterotoxigenic Escherichia coli has an immunoglobulin-like lectin domain that binds N-acetylglucosamine. Mol. Microb. 49, 705-715.</ref><ref>Merckel, M. C., Tanskanen, J., Edelman, S., Westerlund-Wilkström, B., Korhonen, T. K. & Goldman, A. (2003). The structural basis of receptor-binding by Escherichia coli associaed with diarrhea and septicemia. J. Mol. Biol. 331, 897-905.</ref>. Related adhesins have been characterized in enteropathogenic ''E. coli'' ( FedF on F18 fimbriae<ref>Coddens, A., Diswall, M., Angstrom, J., Breimer, M. E., Goddeeris, B., Cox, E. & Teneberg, S. (2009). Recognition of blood group ABH type 1 determinants by the FedF adhesin of F18-fimbriated Escherichia coli. J Biol Chem 284, 9713-26.</ref> and CfaE on CFA/I pili<ref>Poole, S. T., McVeigh, A. L., Anantha, R. P., Lee, L. H., Akay, Y. M., Pontzer, E. A., Scott, D. A., Bullitt, E. & Savarino, S. J. (2007). Donor strand complementation governs intersubunit interaction of fimbriae of the alternate chaperone pathway. Mol Microbiol 63, 1372-84.</ref>) ) and uropathogenic ones (FimH on type 1 fimbriae<ref>Bouckaert, J., Berglund, J., Schembri, M., De Gents, E., Cools, L., Wuhrer, M., Hung, C.-S., Pinkner, J., Slättegard, R., Savialov, A., Choudhury, D., Langermann, S., Hultgren, S. J., Wyns, L., Klemm, P., Oscarson, S., Knight, S. D. & De Greve, H. (2005). Receptor binding studies disclose a novel class of high-affinity inhibitors of the Escherichia coli FimH adhesin. Mol. Microb. 55, 441-455.</ref> and PapG on P-pili<ref>Dodson, K. W., Pinkner, J. S., Rose, T., Magnusson, G., Hultgren, S. J. & Waksman, G. (2001). Structural basis of the interaction of the pyelonephritic E. coli adhesin to ist human kideny receptor. Cell 105, 733-743.</ref>). Fimbrial adhesins from other organisms, such as CupB6 from ''Pseudomonas aeruginosa'' are also investigated. All share the immunoglobulin-like fold of the two structural components, despite lack of any sequence identity and diversity in carbohydrate specificity and binding site, and the corresponding pili are assembled by the chaperone-usher pathway<ref>De Greve, H., Wyns, L. & Bouckaert, J. (2007). Combining sites of bacterial fimbriae. Curr Opin Struct Biol 17, 506-12.</ref><ref>Sauer, F. G., Barnhart, M., Choudhury, D., Knight, S. D., Waksman, G. & Hultgren, S. J. (2000). Chaperone-assisted pilus assembly and bacterial attachment. Curr Opin Struct Biol 10, 548-56.</ref>. The paradigm is unique among TAD for his specificity toward GlcNAc. The binding site is located laterally and not at the tip of the pili, therefore the long and flexible F17 fimbriae could intrude between the microvilli of the epithelium, with the binding site of the lectin domain interacting laterally with GlcNAc-containing receptors. Five naturally occurring variants, differing in 1-18 amino acids of the adhesion domain have been identified<ref>De Kerpel, M., Van Molle, I., Brys, L., Wyns, L., De Greve, H. & Bouckaert, J. (2006). N-terminal truncation enables crystallization of the receptor-binding domain of the FedF bacterial adhesin. Acta Crystallogr Sect F Struct Biol Cryst Commun 62, 1278-82.</ref>.

== CFG Participating Investigators contributing to the understanding of this paradigm ==
This is an emerging field of investigation and contributions arose from a small number of CFG Participating Investigators (PIs). These include: Esther Bullit, Eric Cox, Anne Imberty, Remy Loris, James Nataro

== Progress toward understanding this GBP paradigm ==

=== Carbohydrate ligands ===

<The F17G adhesin is most specific for the disaccharide GlcNAcb1,3Gal that can be recognised as a terminal or internal sequence in bovine glycophorin (<ref>Mouricout, M., Milhavet, M., Durié, C., Grange, P. Characterization of glycoprotein glycan receptors for Escherichia coli F17 fimbrial lectin, Microb. Pathog. (1995) 18, 297-306</ref>): (carbSynthe_0691_D000.jpg) >

=== Cellular expression ===

<F17G adhesins are constitutively expressed on enterotoxigenic E. coli infecting neonatal lambs, calfs and goat kids.>

=== Structure ===

< >

=== Biological roles of GBP-ligand interaction ===

 
== CFG resources used in investigations ==
The best examples of CFG contributions to this paradigm are described below, with links to specific data sets. For a complete list of CFG data and resources relating to this paradigm, see the CFG database search results for [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=fimbriae&maxresults=20 fimbriae] and [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=pili&maxresults=20 pili].

=== Glycan profiling ===

 
=== Glycogene microarray ===

 
=== Knockout mouse lines ===

 
=== Glycan array ===
F17G adhesins have been screened for their glycan specificity: http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=F17G&maxresults=20

The specificity of some of the other fimbrial tip adhesins was determined by CFG glycan array analysis ([http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_2358 ''P. gingivalis'' fimbriae], [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_PA_v2_178_11182005 ''E. coli'' FedF adhesin], [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_1106 ''E. coli'' CfaE adhesin from CFA/I pili])

== Related GBPs ==
FedF, CfaE, FimH, PapG, CupB6

== References ==
<references/>

== Acknowledgements ==
The CFG is grateful to the following PIs for their contributions to this wiki page: Alisdair Boraston, Julie Bouckaert, Anne Imberty

F17G/GafD

2010-06-15T05:33:25Z

Julie Bouckaert: /* Carbohydrate ligands */

The F17-G (GafD) adhesin at the tip of flexible F17 fimbriae of enterotoxigenic ''Escherichia coli'' mediates binding to N-acetyl-β-D-glucosamine-presenting receptors on the microvilli of the intestinal epithelium of ruminants, leading to diarrhea or septicaemia. F17-G belong to two-domain adhesins (TDA)s consisting of a pilin domain and a lectin domain, both having an Ig-fold joined via a short interdomain linker<ref>Buts, L., Bouckaert, J., De Gents, E., Loris, R., Oscarson, S., Lahmann, M., Messens, J., Brosens, E., Wyns, L. & De Greve, H. (2003). The fimbrial adhesin F17-G of enterotoxigenic Escherichia coli has an immunoglobulin-like lectin domain that binds N-acetylglucosamine. Mol. Microb. 49, 705-715.</ref><ref>Merckel, M. C., Tanskanen, J., Edelman, S., Westerlund-Wilkström, B., Korhonen, T. K. & Goldman, A. (2003). The structural basis of receptor-binding by Escherichia coli associaed with diarrhea and septicemia. J. Mol. Biol. 331, 897-905.</ref>. Related adhesins have been characterized in enteropathogenic ''E. coli'' ( FedF on F18 fimbriae<ref>Coddens, A., Diswall, M., Angstrom, J., Breimer, M. E., Goddeeris, B., Cox, E. & Teneberg, S. (2009). Recognition of blood group ABH type 1 determinants by the FedF adhesin of F18-fimbriated Escherichia coli. J Biol Chem 284, 9713-26.</ref> and CfaE on CFA/I pili<ref>Poole, S. T., McVeigh, A. L., Anantha, R. P., Lee, L. H., Akay, Y. M., Pontzer, E. A., Scott, D. A., Bullitt, E. & Savarino, S. J. (2007). Donor strand complementation governs intersubunit interaction of fimbriae of the alternate chaperone pathway. Mol Microbiol 63, 1372-84.</ref>) ) and uropathogenic ones (FimH on type 1 fimbriae<ref>Bouckaert, J., Berglund, J., Schembri, M., De Gents, E., Cools, L., Wuhrer, M., Hung, C.-S., Pinkner, J., Slättegard, R., Savialov, A., Choudhury, D., Langermann, S., Hultgren, S. J., Wyns, L., Klemm, P., Oscarson, S., Knight, S. D. & De Greve, H. (2005). Receptor binding studies disclose a novel class of high-affinity inhibitors of the Escherichia coli FimH adhesin. Mol. Microb. 55, 441-455.</ref> and PapG on P-pili<ref>Dodson, K. W., Pinkner, J. S., Rose, T., Magnusson, G., Hultgren, S. J. & Waksman, G. (2001). Structural basis of the interaction of the pyelonephritic E. coli adhesin to ist human kideny receptor. Cell 105, 733-743.</ref>). Fimbrial adhesins from other organisms, such as CupB6 from ''Pseudomonas aeruginosa'' are also investigated. All share the immunoglobulin-like fold of the two structural components, despite lack of any sequence identity and diversity in carbohydrate specificity and binding site, and the corresponding pili are assembled by the chaperone-usher pathway<ref>De Greve, H., Wyns, L. & Bouckaert, J. (2007). Combining sites of bacterial fimbriae. Curr Opin Struct Biol 17, 506-12.</ref><ref>Sauer, F. G., Barnhart, M., Choudhury, D., Knight, S. D., Waksman, G. & Hultgren, S. J. (2000). Chaperone-assisted pilus assembly and bacterial attachment. Curr Opin Struct Biol 10, 548-56.</ref>. The paradigm is unique among TAD for his specificity toward GlcNAc. The binding site is located laterally and not at the tip of the pili, therefore the long and flexible F17 fimbriae could intrude between the microvilli of the epithelium, with the binding site of the lectin domain interacting laterally with GlcNAc-containing receptors. Five naturally occurring variants, differing in 1-18 amino acids of the adhesion domain have been identified<ref>De Kerpel, M., Van Molle, I., Brys, L., Wyns, L., De Greve, H. & Bouckaert, J. (2006). N-terminal truncation enables crystallization of the receptor-binding domain of the FedF bacterial adhesin. Acta Crystallogr Sect F Struct Biol Cryst Commun 62, 1278-82.</ref>.

== CFG Participating Investigators contributing to the understanding of this paradigm ==
This is an emerging field of investigation and contributions arose from a small number of CFG Participating Investigators (PIs). These include: Esther Bullit, Eric Cox, Anne Imberty, Remy Loris, James Nataro

== Progress toward understanding this GBP paradigm ==

=== Carbohydrate ligands ===

<The F17G adhesin is most specific for the disaccharide GlcNAcb1,3Gal that can be recognised as a terminal or internal sequence in bovine glycophorin (<ref>Mouricout, M., et al., Characterization of glycoprotein glycan receptors for Escherichia coli F17 fimbrial lectin, Microb. Pathog. (1995) 18, 297-306</ref>): (carbSynthe_0691_D000.jpg) >

=== Cellular expression ===

<F17G adhesins are constitutively expressed on enterotoxigenic E. coli infecting neonatal lambs, calfs and goat kids.>

=== Structure ===

< >

=== Biological roles of GBP-ligand interaction ===

 
== CFG resources used in investigations ==
The best examples of CFG contributions to this paradigm are described below, with links to specific data sets. For a complete list of CFG data and resources relating to this paradigm, see the CFG database search results for [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=fimbriae&maxresults=20 fimbriae] and [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=pili&maxresults=20 pili].

=== Glycan profiling ===

 
=== Glycogene microarray ===

 
=== Knockout mouse lines ===

 
=== Glycan array ===
F17G adhesins have been screened for their glycan specificity: http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=F17G&maxresults=20

The specificity of some of the other fimbrial tip adhesins was determined by CFG glycan array analysis ([http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_2358 ''P. gingivalis'' fimbriae], [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_PA_v2_178_11182005 ''E. coli'' FedF adhesin], [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_1106 ''E. coli'' CfaE adhesin from CFA/I pili])

== Related GBPs ==
FedF, CfaE, FimH, PapG, CupB6

== References ==
<references/>

== Acknowledgements ==
The CFG is grateful to the following PIs for their contributions to this wiki page: Alisdair Boraston, Julie Bouckaert, Anne Imberty

F17G/GafD

2010-06-15T05:31:39Z

Julie Bouckaert: /* Carbohydrate ligands */

F17G/GafD

2010-06-15T05:29:56Z

Julie Bouckaert: /* Cellular expression */

F17G/GafD

2010-06-15T05:29:38Z

Julie Bouckaert: /* Structure */

F17G/GafD

2010-06-15T05:29:13Z

Julie Bouckaert: /* Structure */

F17G/GafD

2010-06-15T05:28:14Z

Julie Bouckaert: /* Carbohydrate ligands */

F17G/GafD

2010-06-15T05:10:17Z

Julie Bouckaert: /* Glycan array */