Difference between revisions of "Ficolin M (Ficolin 1)"
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| − | The ficolins are a group of soluble animal proteins with roles in innate immunity<ref>Lu, J. and Le, Y. Ficolins and the fibrinogen-like domain. Immunobiology 199, 190-199 (1998)</ref><ref name="Teh 30">Teh, C., Le, Y., Lee, S. H. and Lu, J. M-ficolin is expressed on monocytes and is a lectin binding to N-acetyl-D-glucosamine and mediates monocyte adhesion and phagocytosis of Escherichia coli. Immunology 101, 225-232 (2000)</ref><ref>Matsushita, M. and Fujita, T. The role of ficolins in innate immunity. Immunobiology 205, 490-497 (2002)</ref><ref name="Endo 32">Endo, Y., Liu, Y. and Fujita, T. Structure and function of ficolins. Adv Exp Med Biol 586, 265-279 (2006) </ref><ref name="Zhang 33">Zhang, X. L. and Ali, M. A. Ficolins: structure, function and associated diseases. Adv Exp Med Biol 632, 105-115 (2008)</ref>. The classification of ficolins as lectins is somewhat controversial since the ligand binding domain in ficolins is specific for acetyl groups in both carbohydrates (e.g. GlcNAc, ManNAc, GalNAc) and non-carbohydrates (eg N-acetylglycine, N-acetylcysteine, acetylcholine)<ref name="Teh 30"/><ref name="Frederiksen 34">Frederiksen, P. D., Thiel, S., Larsen, C. B. and Jensenius, J. C. M-ficolin, an innate immune defence molecule, binds patterns of acetyl groups and activates complement. Scand J Immunol 62, 462-473 (2005)</ref>. Binding of sugars is not primarily dependent on the sugar ring, and sugars that do not contain acetyl groups are generally not ficolin ligands<ref name="Endo 32"/>. However, many of the bacterial surface molecules that appear to be natural ligands for the ficolins contain carbohydrate moieties, and ficolins have similar functional properties to lectins. They are certainly capable of binding acetylated sugars as evidenced by glycan array screening<ref name="Gout 35">Gout, E., Garlatti, V., Smith, D. F., Lacroix, M. M., Dumestre-Perard, C., Lunardi, T., Martin, L., Cesbron, J. Y., Arlaud, G. J., Gaboriaud, C. and Thielens, N. M. Carbohydrate recognition properties of human ficolins: Glycan array screening reveals the sialic acid binding specificity of M-ficolin. J Biol Chem (2009) </ref>. Ficolin M (Ficolin 1) and Ficolin L (Ficolin 2) are the most widely studied<ref name="Zhang 33"/><ref name="Frederiksen 34"/><ref name="Gout 35"/><ref>Liu, Y., Endo, Y., Iwaki, D., Nakata, M., Matsushita, M., Wada, I., Inoue, K., Munakata, M. and Fujita, T. Human M-ficolin is a secretory protein that activates the lectin complement pathway. J Immunol 175, 3150-3156 (2005)</ref><ref>Tanio, M., Kondo, S., Sugio, S. and Kohno, T. Overexpression, purification and preliminary crystallographic analysis of human M-ficolin fibrinogen-like domain. Acta Crystallogr Sect F Struct Biol Cryst Commun 62, 652-655 (2006)</ref><ref>Garlatti, V., Martin, L., Gout, E., Reiser, J. B., Fujita, T., Arlaud, G. J., Thielens, N. M. and Gaboriaud, C. Structural basis for innate immune sensing by M-ficolin and its control by a pH-dependent conformational switch. J Biol Chem 282, 35814-35820 (2007)</ref><ref name="Frankenberger 39">Frankenberger, M., Schwaeble, W. and Ziegler-Heitbrock, L. Expression of M-Ficolin in human monocytes and macrophages. Mol Immunol 45, 1424-1430 (2008)</ref><ref>Honore, C., Rorvig, S., Munthe-Fog, L., Hummelshoj, T., Madsen, H. O., Borregaard, N. and Garred, P. The innate pattern recognition molecule Ficolin-1 is secreted by monocytes/macrophages and is circulating in human plasma. Mol Immunol 45, 2782-2789 (2008)</ref>. Ficolin L is a serum protein produced in the liver that through association with Mannose-binding protein-associated proteases (MASPs) triggers complement activation in response to binding to pathogen surfaces. It also serves as an opsinin triggering phagocytic uptake of pathogens by neutrophils. Polymorphisms in Ficolin L may have pathophysiological implications<ref>Messias-Reason, I. J., Schafranski, M. D., Kremsner, P. G. and Kun, J. F. Ficolin 2 (FCN2) functional polymorphisms and the risk of rheumatic fever and rheumatic heart disease. Clin Exp Immunol 157, 395-399 (2009)</ref>. Ficolin M is produced in the lung and has been examined structurally. Ficolin M is found in secretory granules in neutrophils and monocytes, recognizes pathogens, and also activates complement via MASPs<ref name="Frankenberger 39"/>. | + | The ficolins are a group of soluble animal proteins with roles in innate immunity<ref>Lu, J. and Le, Y. Ficolins and the fibrinogen-like domain. Immunobiology 199, 190-199 (1998)</ref><ref name="Teh 30">Teh, C., Le, Y., Lee, S. H. and Lu, J. M-ficolin is expressed on monocytes and is a lectin binding to N-acetyl-D-glucosamine and mediates monocyte adhesion and phagocytosis of Escherichia coli. Immunology 101, 225-232 (2000)</ref><ref>Matsushita, M. and Fujita, T. The role of ficolins in innate immunity. Immunobiology 205, 490-497 (2002)</ref><ref name="Endo 32">Endo, Y., Liu, Y. and Fujita, T. Structure and function of ficolins. Adv Exp Med Biol 586, 265-279 (2006) </ref><ref name="Zhang 33">Zhang, X. L. and Ali, M. A. Ficolins: structure, function and associated diseases. Adv Exp Med Biol 632, 105-115 (2008)</ref>. The classification of ficolins as lectins is somewhat controversial since the ligand binding domain in ficolins is specific for acetyl groups in both carbohydrates (e.g. GlcNAc, ManNAc, GalNAc) and non-carbohydrates (eg N-acetylglycine, N-acetylcysteine, acetylcholine)<ref name="Teh 30"/><ref name="Frederiksen 34">Frederiksen, P. D., Thiel, S., Larsen, C. B. and Jensenius, J. C. M-ficolin, an innate immune defence molecule, binds patterns of acetyl groups and activates complement. Scand J Immunol 62, 462-473 (2005)</ref>. Binding of sugars is not primarily dependent on the sugar ring, and sugars that do not contain acetyl groups are generally not ficolin ligands<ref name="Endo 32"/>. However, many of the bacterial surface molecules that appear to be natural ligands for the ficolins contain carbohydrate moieties, and ficolins have similar functional properties to lectins. They are certainly capable of binding acetylated sugars as evidenced by glycan array screening<ref name="Gout 35">Gout, E., Garlatti, V., Smith, D. F., Lacroix, M. M., Dumestre-Perard, C., Lunardi, T., Martin, L., Cesbron, J. Y., Arlaud, G. J., Gaboriaud, C. and Thielens, N. M. Carbohydrate recognition properties of human ficolins: Glycan array screening reveals the sialic acid binding specificity of M-ficolin. J Biol Chem (2009) </ref>. Ficolin M (Ficolin 1) and Ficolin L (Ficolin 2) are the most widely studied<ref name="Zhang 33"/><ref name="Frederiksen 34"/><ref name="Gout 35"/><ref name="Liu 2005">Liu, Y., Endo, Y., Iwaki, D., Nakata, M., Matsushita, M., Wada, I., Inoue, K., Munakata, M. and Fujita, T. Human M-ficolin is a secretory protein that activates the lectin complement pathway. J Immunol 175, 3150-3156 (2005)</ref><ref name="Tanio 2006">Tanio, M., Kondo, S., Sugio, S. and Kohno, T. Overexpression, purification and preliminary crystallographic analysis of human M-ficolin fibrinogen-like domain. Acta Crystallogr Sect F Struct Biol Cryst Commun 62, 652-655 (2006)</ref><ref name="Garlatti 2007">Garlatti, V., Martin, L., Gout, E., Reiser, J. B., Fujita, T., Arlaud, G. J., Thielens, N. M. and Gaboriaud, C. Structural basis for innate immune sensing by M-ficolin and its control by a pH-dependent conformational switch. J Biol Chem 282, 35814-35820 (2007)</ref><ref name="Frankenberger 39">Frankenberger, M., Schwaeble, W. and Ziegler-Heitbrock, L. Expression of M-Ficolin in human monocytes and macrophages. Mol Immunol 45, 1424-1430 (2008)</ref><ref name="Honore 2008">Honore, C., Rorvig, S., Munthe-Fog, L., Hummelshoj, T., Madsen, H. O., Borregaard, N. and Garred, P. The innate pattern recognition molecule Ficolin-1 is secreted by monocytes/macrophages and is circulating in human plasma. Mol Immunol 45, 2782-2789 (2008)</ref>. Ficolin L is a serum protein produced in the liver that through association with Mannose-binding protein-associated proteases (MASPs) triggers complement activation in response to binding to pathogen surfaces. It also serves as an opsinin triggering phagocytic uptake of pathogens by neutrophils. Polymorphisms in Ficolin L may have pathophysiological implications<ref>Messias-Reason, I. J., Schafranski, M. D., Kremsner, P. G. and Kun, J. F. Ficolin 2 (FCN2) functional polymorphisms and the risk of rheumatic fever and rheumatic heart disease. Clin Exp Immunol 157, 395-399 (2009)</ref>. Ficolin M is produced in the lung and has been examined structurally. Ficolin M is found in secretory granules in neutrophils and monocytes, recognizes pathogens, and also activates complement via MASPs<ref name="Frankenberger 39"/>. |
See also: paradigm page for [[Ficolins/Mannose-binding protein]] | See also: paradigm page for [[Ficolins/Mannose-binding protein]] | ||
| Line 6: | Line 6: | ||
== Progress toward understanding this GBP paradigm == | == Progress toward understanding this GBP paradigm == | ||
| + | This section documents what is currently known about Ficolin M, its carbohydrate ligand(s), and how they interact to mediate cell communication. | ||
| + | === Carbohydrate ligands === | ||
| + | |||
| + | M-ficolin preferentially binds to 9-O-acetylated 2-6-linked sialic acid derivatives and to various glycans containing sialic acid engaged in α 2-3 linkage, including gangliosides<ref name="Gout 35"/>. | ||
| − | === | + | === Cellular expression of GBP and ligands === |
| + | M-ficolin has been localized at the surface of blood monocytes and in secretory granules of neutrophils, monocytes, and lung epithelial cells<ref name="Teh 30"/><ref name="Frederiksen 34"/><ref name="Liu 2005"/>. However, two recent studies have reported its detection in serum, with mean concentrations ranging from 0.06 to 1 μg/ml<ref name="Honore 2008"/><ref>Wittenborn, T., Thiel, S., Jensen, L., Nielsen, H. J., and Jensenius, J. C. Characteristics and biological variations of M-ficolin, a pattern recognition molecule, in plasma. J Innate Immun 2, 167-180 (2010)</ref>. | ||
| − | + | === Biosynthesis of ligands === | |
| − | === | + | Pathways for ganglioside biosynthesis have been described ([http://www.functionalglycomics.org/glycomics/molecule/jsp/glycoEnzyme/geMolecule.jsp GT Database]). |
| + | <br>O-acetylation at positions C-7,8,9 of sialic acid is catalyzed by O-acetyltransferase enzymes associated with the Golgi membrane in mammals<ref>Higa, H.H., Manzi, A. and Varki, A. O-acetylation and de-O-acetylation of sialic acids. Purification, characterization, and properties of a glycosylated rat liver esterase specific for 9-O-acetylated sialic acids. J Biol Chem 264, 19435-19442 (1989)</ref><ref>Butor, C., Higa, H.H. and Varki, A. Structural, immunological, and biosynthetic studies of a sialic acid-specific O-acetylesterase from rat liver. J Biol Chem 268, 10207-10213 (1993)</ref>. Sialic acid O-acetyltransferases have also been identified in bacteria, but they are not homologous to the vertebrate enzymes<ref>Lewis, A.L., Hensler, M.E., Varki, A. and Nizet, V. The group B streptococcal sialic acid O-acetyltransferase is encoded by neuD, a conserved component of bacterial sialic acid biosynthetic gene clusters. J Biol Chem 281, 11186-11192 (2006)</ref>. | ||
| − | |||
=== Structure === | === Structure === | ||
| − | < | + | The structure of the trimeric fibrinogen-like recognition domain of M-ficolin, alone and in complex with various acetylated ligands, has been solved by X-ray crystallography<ref name="Tanio 2006"/><ref name="Garlatti 2007"/>. A single ligand binding site was observed, located close to the calcium-binding site in the outer part of the trimer and homologous to the GlcNAc binding pocket of the invertebrate tachylectin TL5A <ref>Kairies, N., Beisel, H. G., Fuentes-Prior, P., Tsuda, R., Muta, T., Iwanaga, S., Bode, W., Huber, R., and Kawabata, S. I. Proc. Natl. Acad. Sci. U.S.A. 98, 13519–13524 (2001)</ref>. The essential role of Tyr 271 in the binding specificity for sialic acid was further demonstrated using site-directed mutagenesis<ref name="Gout 35"/>. |
| + | |||
=== Biological roles of GBP-ligand interaction === | === Biological roles of GBP-ligand interaction === | ||
| − | < | + | Soluble M-ficolin has been shown to bind to ''Staphylococcus aureus'' through GlcNAc<ref name="Liu 2005"/>. It is tethered to monocytes and granulocytes through binding of its fibrinogen-like recognition domain to sialic acid on the cell surface<ref>Honore C, Rorvig S, Hummelshoj T, Skjoedt MO, Borregaard N, and Garred P. Tethering of Ficolin-1 to cell surfaces through recognition of sialic acid by the fibrinogen-like domain. J Leukoc Biol 88, 145-158 (2010)</ref>. |
| + | |||
== CFG resources used in investigations == | == 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 [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=ficolin&maxresults=20 CFG database search results for ficolin]. | 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 [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=ficolin&maxresults=20 CFG database search results for ficolin]. | ||
=== Glycan profiling === | === Glycan profiling === | ||
| + | Glycan profiling has not been performed. | ||
| + | <br> | ||
| + | === Glycogene microarray === | ||
| + | No data available. | ||
<br> | <br> | ||
| − | |||
| − | |||
=== Knockout mouse lines === | === Knockout mouse lines === | ||
| Line 33: | Line 42: | ||
=== Glycan array === | === Glycan array === | ||
The soluble ficolins have been extensively examined using the CFG glycan array ([http://www.functionalglycomics.org/glycomics/search/jsp/result.jsp?query=ficolin&cat=coreh 28 screens]). | The soluble ficolins have been extensively examined using the CFG glycan array ([http://www.functionalglycomics.org/glycomics/search/jsp/result.jsp?query=ficolin&cat=coreh 28 screens]). | ||
| + | <br>Human M-ficolin | ||
| + | investigators have used CFG glycan arrays to study the ligand binding specificity of human recombinant wild-type M-ficolin at various concentrations (click [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_1602 here], [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_2417 here], [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_2123 here], [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_2124 here], [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_2412 here], [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_2418 here], and [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_2419 here]), and of 4 variants with the following point mutations in the recognition domain: G221F (click [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_2413 here], [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_2420 here], and [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_2421 here]), A256V (click [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_2414 here], [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_2422 here], and [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_2423 here]), G221F/A256V (click [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_2415 here]) and Y271F (click [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_2416 here] and [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_2417 here]). The binding specificity of the rat homologue of M-ficolin, ficolin B, has also been investigated using CFG glycan arrays (click [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_1708 here] and [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_1768 here]). | ||
== Related GBPs == | == Related GBPs == | ||
| − | This family is characterized by the presence of a leader peptide, a short N-terminal segment, followed by a collagen-like region, and a C-terminal fibrinogen-like domain. Homologs are apparently absent in ''D. melanogaster'' and ''C. elegans''. Several human family members have been described but Ficolin L and M are the best characterized both biochemically and structurally. Ficolin L and H are made in the liver, while Ficolin M and H are produced by the lung. Two ficolins (A and B) are present in mouse. Ficolin B may be the ortholog of Ficolin M. | + | This family is characterized by the presence of a leader peptide, a short N-terminal segment, followed by a collagen-like region, and a C-terminal fibrinogen-like domain. Homologs are apparently absent in ''D. melanogaster'' and ''C. elegans''. Several human family members have been described but Ficolin L and M are the best characterized both biochemically and structurally. Ficolin L [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=ficolin+AND+L&maxresults=20 (CFG data)] and H [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=ficolin+AND+H&maxresults=20 (CFG data)] are made in the liver, while Ficolin M and H are produced by the lung. Two ficolins (A and B) are present in mouse. Ficolin B may be the ortholog of Ficolin M. |
| + | <br>A vertebrate membrane-bound chitin-binding protein, called FIBCD1 (Fibrinogen C domain containing 1) has been identified recently<ref>Schlosser A, Thomsen T, Moeller JB, Nielsen O, Tornoe I, Mollenhauer J, Moestrup SK, and Holmskov U. Characterization of FIBCD1 as an acetyl group-binding receptor that binds chitin. J Immunol 183, 3800-3809 (2009)</ref>. The ectodomain of FIBCD1 forms disulfide-linked tetramers assembled from a coiled-coil region, a polycationic region and a C-terminal fibrinogen-related domain. The acetyl-binding site of the fibrinogen-like recognition domain of FIBCD1 is homologous to that of TL5A and M-ficolin<ref> Thomsen T, Moeller JB, Schlosser A, Sorensen GL, Moestrup SK, Palaniyar N, Wallis R, Mollenhauer J, and Holmskov U. The recognition unit of FIBCD1 organizes into a non-covalently linked tetrameric structure and uses a hydrophobic funnel (S1) for acetyl group recognition. J Biol Chem 285, 1229-1028 (2010)</ref>. | ||
== References == | == References == | ||
Latest revision as of 19:07, 28 March 2011
The ficolins are a group of soluble animal proteins with roles in innate immunity[1][2][3][4][5]. The classification of ficolins as lectins is somewhat controversial since the ligand binding domain in ficolins is specific for acetyl groups in both carbohydrates (e.g. GlcNAc, ManNAc, GalNAc) and non-carbohydrates (eg N-acetylglycine, N-acetylcysteine, acetylcholine)[2][6]. Binding of sugars is not primarily dependent on the sugar ring, and sugars that do not contain acetyl groups are generally not ficolin ligands[4]. However, many of the bacterial surface molecules that appear to be natural ligands for the ficolins contain carbohydrate moieties, and ficolins have similar functional properties to lectins. They are certainly capable of binding acetylated sugars as evidenced by glycan array screening[7]. Ficolin M (Ficolin 1) and Ficolin L (Ficolin 2) are the most widely studied[5][6][7][8][9][10][11][12]. Ficolin L is a serum protein produced in the liver that through association with Mannose-binding protein-associated proteases (MASPs) triggers complement activation in response to binding to pathogen surfaces. It also serves as an opsinin triggering phagocytic uptake of pathogens by neutrophils. Polymorphisms in Ficolin L may have pathophysiological implications[13]. Ficolin M is produced in the lung and has been examined structurally. Ficolin M is found in secretory granules in neutrophils and monocytes, recognizes pathogens, and also activates complement via MASPs[11].
See also: paradigm page for Ficolins/Mannose-binding protein
CFG Participating Investigators contributing to the understanding of this paradigm
Investigators using CFG resources to study ficolins include: Raymond Dwek, Daniel Mitchell, Nicole Thielens
Progress toward understanding this GBP paradigm
This section documents what is currently known about Ficolin M, its carbohydrate ligand(s), and how they interact to mediate cell communication.
Carbohydrate ligands
M-ficolin preferentially binds to 9-O-acetylated 2-6-linked sialic acid derivatives and to various glycans containing sialic acid engaged in α 2-3 linkage, including gangliosides[7].
Cellular expression of GBP and ligands
M-ficolin has been localized at the surface of blood monocytes and in secretory granules of neutrophils, monocytes, and lung epithelial cells[2][6][8]. However, two recent studies have reported its detection in serum, with mean concentrations ranging from 0.06 to 1 μg/ml[12][14].
Biosynthesis of ligands
Pathways for ganglioside biosynthesis have been described (GT Database).
O-acetylation at positions C-7,8,9 of sialic acid is catalyzed by O-acetyltransferase enzymes associated with the Golgi membrane in mammals[15][16]. Sialic acid O-acetyltransferases have also been identified in bacteria, but they are not homologous to the vertebrate enzymes[17].
Structure
The structure of the trimeric fibrinogen-like recognition domain of M-ficolin, alone and in complex with various acetylated ligands, has been solved by X-ray crystallography[9][10]. A single ligand binding site was observed, located close to the calcium-binding site in the outer part of the trimer and homologous to the GlcNAc binding pocket of the invertebrate tachylectin TL5A [18]. The essential role of Tyr 271 in the binding specificity for sialic acid was further demonstrated using site-directed mutagenesis[7].
Biological roles of GBP-ligand interaction
Soluble M-ficolin has been shown to bind to Staphylococcus aureus through GlcNAc[8]. It is tethered to monocytes and granulocytes through binding of its fibrinogen-like recognition domain to sialic acid on the cell surface[19].
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 ficolin.
Glycan profiling
Glycan profiling has not been performed.
Glycogene microarray
No data available.
Knockout mouse lines
Glycan array
The soluble ficolins have been extensively examined using the CFG glycan array (28 screens).
Human M-ficolin
investigators have used CFG glycan arrays to study the ligand binding specificity of human recombinant wild-type M-ficolin at various concentrations (click here, here, here, here, here, here, and here), and of 4 variants with the following point mutations in the recognition domain: G221F (click here, here, and here), A256V (click here, here, and here), G221F/A256V (click here) and Y271F (click here and here). The binding specificity of the rat homologue of M-ficolin, ficolin B, has also been investigated using CFG glycan arrays (click here and here).
Related GBPs
This family is characterized by the presence of a leader peptide, a short N-terminal segment, followed by a collagen-like region, and a C-terminal fibrinogen-like domain. Homologs are apparently absent in D. melanogaster and C. elegans. Several human family members have been described but Ficolin L and M are the best characterized both biochemically and structurally. Ficolin L (CFG data) and H (CFG data) are made in the liver, while Ficolin M and H are produced by the lung. Two ficolins (A and B) are present in mouse. Ficolin B may be the ortholog of Ficolin M.
A vertebrate membrane-bound chitin-binding protein, called FIBCD1 (Fibrinogen C domain containing 1) has been identified recently[20]. The ectodomain of FIBCD1 forms disulfide-linked tetramers assembled from a coiled-coil region, a polycationic region and a C-terminal fibrinogen-related domain. The acetyl-binding site of the fibrinogen-like recognition domain of FIBCD1 is homologous to that of TL5A and M-ficolin[21].
References
- ↑ Lu, J. and Le, Y. Ficolins and the fibrinogen-like domain. Immunobiology 199, 190-199 (1998)
- ↑ 2.0 2.1 2.2 Teh, C., Le, Y., Lee, S. H. and Lu, J. M-ficolin is expressed on monocytes and is a lectin binding to N-acetyl-D-glucosamine and mediates monocyte adhesion and phagocytosis of Escherichia coli. Immunology 101, 225-232 (2000)
- ↑ Matsushita, M. and Fujita, T. The role of ficolins in innate immunity. Immunobiology 205, 490-497 (2002)
- ↑ 4.0 4.1 Endo, Y., Liu, Y. and Fujita, T. Structure and function of ficolins. Adv Exp Med Biol 586, 265-279 (2006)
- ↑ 5.0 5.1 Zhang, X. L. and Ali, M. A. Ficolins: structure, function and associated diseases. Adv Exp Med Biol 632, 105-115 (2008)
- ↑ 6.0 6.1 6.2 Frederiksen, P. D., Thiel, S., Larsen, C. B. and Jensenius, J. C. M-ficolin, an innate immune defence molecule, binds patterns of acetyl groups and activates complement. Scand J Immunol 62, 462-473 (2005)
- ↑ 7.0 7.1 7.2 7.3 Gout, E., Garlatti, V., Smith, D. F., Lacroix, M. M., Dumestre-Perard, C., Lunardi, T., Martin, L., Cesbron, J. Y., Arlaud, G. J., Gaboriaud, C. and Thielens, N. M. Carbohydrate recognition properties of human ficolins: Glycan array screening reveals the sialic acid binding specificity of M-ficolin. J Biol Chem (2009)
- ↑ 8.0 8.1 8.2 Liu, Y., Endo, Y., Iwaki, D., Nakata, M., Matsushita, M., Wada, I., Inoue, K., Munakata, M. and Fujita, T. Human M-ficolin is a secretory protein that activates the lectin complement pathway. J Immunol 175, 3150-3156 (2005)
- ↑ 9.0 9.1 Tanio, M., Kondo, S., Sugio, S. and Kohno, T. Overexpression, purification and preliminary crystallographic analysis of human M-ficolin fibrinogen-like domain. Acta Crystallogr Sect F Struct Biol Cryst Commun 62, 652-655 (2006)
- ↑ 10.0 10.1 Garlatti, V., Martin, L., Gout, E., Reiser, J. B., Fujita, T., Arlaud, G. J., Thielens, N. M. and Gaboriaud, C. Structural basis for innate immune sensing by M-ficolin and its control by a pH-dependent conformational switch. J Biol Chem 282, 35814-35820 (2007)
- ↑ 11.0 11.1 Frankenberger, M., Schwaeble, W. and Ziegler-Heitbrock, L. Expression of M-Ficolin in human monocytes and macrophages. Mol Immunol 45, 1424-1430 (2008)
- ↑ 12.0 12.1 Honore, C., Rorvig, S., Munthe-Fog, L., Hummelshoj, T., Madsen, H. O., Borregaard, N. and Garred, P. The innate pattern recognition molecule Ficolin-1 is secreted by monocytes/macrophages and is circulating in human plasma. Mol Immunol 45, 2782-2789 (2008)
- ↑ Messias-Reason, I. J., Schafranski, M. D., Kremsner, P. G. and Kun, J. F. Ficolin 2 (FCN2) functional polymorphisms and the risk of rheumatic fever and rheumatic heart disease. Clin Exp Immunol 157, 395-399 (2009)
- ↑ Wittenborn, T., Thiel, S., Jensen, L., Nielsen, H. J., and Jensenius, J. C. Characteristics and biological variations of M-ficolin, a pattern recognition molecule, in plasma. J Innate Immun 2, 167-180 (2010)
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Acknowledgements
The CFG is grateful to the following PIs for their contributions to this wiki page: John Hanover, Nicole Thielens
