Candida glabrata EPA7 - Revision history

Kurt Drickamer: /* Biosynthesis of ligands */

2011-10-30T20:13:23Z

Biosynthesis of ligands

Kurt Drickamer: /* Biosynthesis of ligands */

2011-10-30T19:25:25Z

Biosynthesis of ligands

Kurt Drickamer: /* Biosynthesis of ligands */

2011-10-30T19:24:47Z

Biosynthesis of ligands

Kurt Drickamer at 19:16, 30 October 2011

2011-10-30T19:16:06Z

Kurt Drickamer: /* Biosynthesis of ligands */

2011-10-02T18:10:40Z

Biosynthesis of ligands

Carole Weaver: /* Knockout mouse lines */

2011-09-15T18:55:43Z

Knockout mouse lines

Carole Weaver: /* Glycogene microarray */

2011-09-15T18:55:33Z

Glycogene microarray

Carole Weaver: /* Related GBPs */

2011-03-22T17:50:08Z

Related GBPs

Carole Weaver at 22:01, 21 September 2010

2010-09-21T22:01:07Z

Carole Weaver at 21:48, 21 September 2010

2010-09-21T21:48:13Z

@@ Line 23: / Line 23: @@
 === Biosynthesis of ligands ===
-On mucins, the T (Gal&beta;1-3GalNAc&alpha;1-Thr/Ser) target ligand for EPA7 is generated by the action of a family of polypeptide O-GalNAc transferases followed by addition of galactose by galactosyltransferase. Transferases T1, T2, T3 and T4 have been suggested to be particularly important in colonic mucin glycosylation.
+On mucins, the T (Gal&beta;1-3GalNAc&alpha;1-Thr/Ser) target ligand for EPA7 is generated by the action of a family of polypeptide O-GalNAc transferases followed by addition of galactose by [http://www.functionalglycomics.org/glycomics/molecule/jsp/glycoEnzyme/viewGlycoEnzyme.jsp?gbpId=gt_hum_447&sideMenu=true&pageType=general galactosyltransferase]. Transferases T1, T2, T3 and T4 have been suggested to be particularly important in colonic mucin glycosylation.
 <br>

@@ Line 23: / Line 23: @@
 === Biosynthesis of ligands ===
-On mucins, the T (Gal&beta;1-3GalNAc&alpha;1-Thr/Ser) target ligand for EPA7 is generated by the action of a family of polypeptide O-GalNAc transferases followed by addition of galactose by galactosyltransferase. Transferases T1, T2, T3 and T4 have been suggested to be particularly important in mucin glycosylation.
+On mucins, the T (Gal&beta;1-3GalNAc&alpha;1-Thr/Ser) target ligand for EPA7 is generated by the action of a family of polypeptide O-GalNAc transferases followed by addition of galactose by galactosyltransferase. Transferases T1, T2, T3 and T4 have been suggested to be particularly important in colonic mucin glycosylation.
 <br>

@@ Line 23: / Line 23: @@
 === Biosynthesis of ligands ===
-On mucins, the Tn (GalNAc&alpha;1-Thr/Ser) target ligand for EPA7 is generated by the action of a family of polypeptide O-GalNAc transferases. Transferases T1, T2, T3 and T4 have been suggested to be particularly important in mucin glycosylation.
+On mucins, the T (Gal&beta;1-3GalNAc&alpha;1-Thr/Ser) target ligand for EPA7 is generated by the action of a family of polypeptide O-GalNAc transferases followed by addition of galactose by galactosyltransferase. Transferases T1, T2, T3 and T4 have been suggested to be particularly important in mucin glycosylation.
 <br>

@@ Line 5: / Line 5: @@
 The EPA family was chosen as a paradigm because of its relevance to a fungal pathogen that affects human health that can be studied in mouse models of infection. EPA7 was chosen to represent this group because it has been demonstrated to function as an adhesin<ref name="Castano 2005"/> and is one of the EPA proteins that has been studied in the most detail. The N-terminal binding domain of this protein, expressed on the surface of S''. cerevisiae'', has been analyzed on the CFG glycan array. These studies demonstrated EPA7 binding specificity for β1,3- and β1,4-linked galactosides
 <ref name=" Zupancic, M.L., 2008">
-Zupancic, M.L., Frieman, M., Smith, D., Alvarez, R.A., Cummings, R.D. and Cormack, B.P. 2008. Glycan microarray analysis of Candida glabrata adhesin ligand specificity. Mol Microbiol, 58, 547-559.</ref><ref>de Groot, P.W.J. and Klis, F.M. 2008. The conserved PA14 domain of cell wall-associated fungal adhesins governs their glycan-binding specificity. Mol Microbiol, 68, 535-537. </ref>. This work represents a significant step forward in the area of lectin-like fungal adhesins; in general the specificity of these important proteins remains unexplored.
+Zupancic, M.L., Frieman, M., Smith, D., Alvarez, R.A., Cummings, R.D. and Cormack, B.P. 2008. Glycan microarray analysis of Candida glabrata adhesin ligand specificity. Mol Microbiol, 68, 547-559.</ref><ref>de Groot, P.W.J. and Klis, F.M. 2008. The conserved PA14 domain of cell wall-associated fungal adhesins governs their glycan-binding specificity. Mol Microbiol, 68, 535-537. </ref>. This work represents a significant step forward in the area of lectin-like fungal adhesins; in general the specificity of these important proteins remains unexplored.
 == CFG Participating Investigators contributing to the understanding of this paradigm ==

@@ Line 23: / Line 23: @@
 === Biosynthesis of ligands ===
 <br>
 === Structure ===

@@ Line 46: / Line 46: @@
 === Knockout mouse lines ===
-<br>CFG knockout mouse lines have not been used for studies pertaining to this paradigm. Examining ''C. glabrata'' infection using wild type and ''epa'' mutant strains in mice with defects in terminal galactosylation could potentially be of interest.
+CFG knockout mouse lines have not been used for studies pertaining to this paradigm. Examining ''C. glabrata'' infection using wild type and ''epa'' mutant strains in mice with defects in terminal galactosylation could potentially be of interest.
 === Glycan array ===

@@ Line 42: / Line 42: @@
 === Glycogene microarray ===
 Mammalian glycogene profiling has not been performed for this paradigm of a fungal protein. Although yeast binding to mammalian cells could conceivably trigger changes in glycogene expression, the critical issue for this adhesin is which glycans are present on the mammalian cell surface upon initial contact. These structures will  mediate the cell:cell interactions that are important for establishment of infection.
 === Knockout mouse lines ===

@@ Line 56: / Line 56: @@
 * Related proteins in ''S. cerevisiae''
 * EPA7-like glycan-binding domain also occurs in predicted proteins of ''Ashbya gossypii'' and ''Kluyveromyces lactis''.
 == References ==

@@ Line 19: / Line 19: @@
 === Cellular expression of GBP and ligands ===
-EPA7 is expressed by the pathogenic fungus ''Candida glabrata''. The EPA gene family is subject to an interesting mechanism of regulation mediated by telomeric silencing. This silencing is relieved in low niacin, leading to increased protein expression. Because urine provides a low niacin growth environment, these adhesins are upregulated in precisely the niche where ''C. glabrata'' must adhere to cause urinary tract infections.
+EPA7 is expressed by the pathogenic fungus ''Candida glabrata''. The EPA gene family is subject to an interesting mechanism of regulation mediated by telomeric silencing. This silencing is relieved in low niacin, leading to increased protein expression. Because urine provides a low niacin growth environment, these adhesins are upregulated in precisely the niche where ''C. glabrata'' must adhere to cause urinary tract infections. <br>
 === Biosynthesis of ligands ===
 === Structure ===