C. difficile toxin A (TcdA) - Revision history

Kurt Drickamer: /* Biosynthesis of ligands */

2011-10-29T12:06:05Z

Biosynthesis of ligands

Carole Weaver at 22:29, 13 September 2011

2011-09-13T22:29:03Z

Carole Weaver: /* Glycogene microarray */

2011-03-30T23:23:07Z

Glycogene microarray

Carole Weaver: /* Glycogene microarray */

2011-03-28T19:11:26Z

Glycogene microarray

Carole Weaver: /* Knockout mouse lines */

2011-03-21T19:51:20Z

Knockout mouse lines

Carole Weaver: /* Related GBPs */

2011-03-21T19:51:08Z

Related GBPs

Ken Ng: /* Structure */

2010-12-17T14:18:58Z

Structure

Ken Ng: /* Structure */

2010-12-17T14:16:57Z

Structure

Ken Ng: /* Structure */

2010-12-17T14:13:58Z

Structure

Ken Ng at 14:12, 17 December 2010

2010-12-17T14:12:37Z

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 TcdA binds the fucosylated blood group antigens Lewis<sup>x</sup> and Lewis<sup>y</sup>, which are present in human intestinal epithelium<ref name="Voth 2005"/> (see above).
 === Biosynthesis of ligands ===
 === Structure ===
 Members of the LCT family are single-chain protein toxins with receptor-binding, translocation and catalysis domains, which mediate cell entry via receptor-mediated endocytosis, translocation into the cytoplasm, and enzymatic cytotoxic activity, respectively. Up to one third of the LCT molecule is comprised of the C-terminal receptor-binding domain, which contains repetitive peptide elements called combined repetitive oligopeptides (CROPs).

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 TcdA is produced by ''Clostridium difficile''. Structurally and functionally related exotoxins in the LCT family are produced by ''C. sordellii'' (lethal and hemorrhagic toxin) and ''C. novyi'' (alpha-toxin).
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 === Biosynthesis of ligands ===

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 === Glycogene microarray ===
-Not applicable, as the CFG microarrays only contain probes for mouse and human glycogenes.
+TcdA is not represented on the CFG microarrays, which only contain probes for mouse and human glycogenes.
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 <br>
 === Glycogene microarray ===
 === Knockout mouse lines ===
 Not applicable.

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 <br>
 === Knockout mouse lines ===
 === Glycan array ===
 The CFG glycan array has been used to examine the [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_2693 glycan-binding specificity of TcdA]. In addition, the CFG's glycan synthesis capability is being used to prepare synthetic oligosaccharides indentified in the glycan array screens (with or without biotin tags) to further probe TcdA-receptor interactions.

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 == Related GBPs ==
-''C. difficile'' toxin B (TcdB), ''C. sordellii'' lethal toxin and hemorrhagic toxin, ''C. novyi'' alpha-toxin.
+''C. difficile'' toxin B (TcdB; [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=TcdB&maxresults=20 CFG data]), ''C. sordellii'' lethal toxin and hemorrhagic toxin, ''C. novyi'' alpha-toxin.
 == References ==

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 Crystallographic structures of several recombinant fragments from the highly repetitive C-terminal domain have revealed an extended beta-solenoid structure that presents seven binding sites for complex oligosaccharide receptors. The bulk of this carbohydrate-binding domain is comprised of multiple copies of short repeats that interspersed with single copies of long repeats. Carbohydrate-binding sites appear to be formed at the junctions of long repeats and the preceding and following short repeats.
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-Crystallographic structures of recombinant fragments of TcdA have been determined with oligosaccharides, including the Gal-alpha(1,3)-LacNAc trisaccharide shown below<ref name = "Greco 2006">Greco, A et al. (2006). Carbohydrate recognition by ''Clostridium difficile'' toxin A. Nat. Struct. Mol. Biol. 13:460-461.</ref>. This trisaccharide was determined to be a likely native receptor for TcdA in the brush border membranes of intestinal epithelial cells from hamster<ref name = "Krivan 1986">Krivan, HC et al (1986). Cell-surface binding site for ''Clostridium difficile'' enterotoxin: evidence for a glycoconjugate containing the sequence Galalpha1,3-Galbeta1,4-GlcNAc. Infect. Imm. 53:573-581.</ref>, an organism which is susceptible to ''C. difficile'' infection (CDI) and is often used as a model for studying the disease.
+Crystallographic structures of recombinant fragments of TcdA have been determined with oligosaccharides, including the Gal-&alpha;(1,3)-LacNAc trisaccharide shown below<ref name = "Greco 2006">Greco, A et al. (2006). Carbohydrate recognition by ''Clostridium difficile'' toxin A. Nat. Struct. Mol. Biol. 13:460-461.</ref>. This trisaccharide was determined to be a likely native receptor for TcdA in the brush border membranes of intestinal epithelial cells from hamster<ref name = "Krivan 1986">Krivan, HC et al (1986). Cell-surface binding site for ''Clostridium difficile'' enterotoxin: evidence for a glycoconjugate containing the sequence Gal&alpha;1,3-Gal&beta;1,4-GlcNAc. Infect. Imm. 53:573-581.</ref>, an organism which is susceptible to ''C. difficile'' infection (CDI) and is often used as a model for studying the disease.
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 [[File:CD_fig1.png]]