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| | ==Vibrio Cholerae Cytolysin Beta-Prism Domain With Methyl-Alpha-Mannose Bound== | | ==Vibrio Cholerae Cytolysin Beta-Prism Domain With Methyl-Alpha-Mannose Bound== |
| - | <StructureSection load='4gx7' size='340' side='right' caption='[[4gx7]], [[Resolution|resolution]] 2.85Å' scene=''> | + | <StructureSection load='4gx7' size='340' side='right'caption='[[4gx7]], [[Resolution|resolution]] 2.85Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4gx7]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Vibrio_cholerae_12129(1) Vibrio cholerae 12129(1)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GX7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GX7 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4gx7]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Vibrio_cholerae_12129(1) Vibrio cholerae 12129(1)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GX7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GX7 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MMA:O1-METHYL-MANNOSE'>MMA</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.85Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1xez|1xez]], [[3o44|3o44]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MMA:O1-METHYL-MANNOSE'>MMA</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HlyA, VCG_000884 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=592313 Vibrio cholerae 12129(1)])</td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4gx7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gx7 OCA], [https://pdbe.org/4gx7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gx7 RCSB], [https://www.ebi.ac.uk/pdbsum/4gx7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gx7 ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4gx7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gx7 OCA], [http://pdbe.org/4gx7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4gx7 RCSB], [http://www.ebi.ac.uk/pdbsum/4gx7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4gx7 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/HLYA_VIBCH HLYA_VIBCH] Bacterial hemolysin that causes cytolysis by forming heptameric pores in target host membranes.<ref>PMID:15978620</ref> |
| - | Pathogens selectively target host cells using adhesion molecules and secreted virulence factors that may utilize protein, lipid, or carbohydrate ligands on the cell surface. The human intestinal pathogen Vibrio cholerae secretes a pore-forming toxin, V.cholerae cytolysin (VCC), which contains two domains that are structurally similar to known carbohydrate-binding proteins. These tandem domains are attached to the carboxy-terminus of the cytolytic domain and contain a beta-trefoil fold and a beta-prism fold. VCC has been shown to bind glycosylated proteins, and removal of the beta-prism domain leads to a large decrease in lytic activity against rabbit erythrocytes. Despite these clues, the identity of the glycan receptors of VCC and the role of glycan binding in toxin activity remain unknown. To better understand this specificity, we used a combination of structural and functional approaches to characterize the carbohydrate-binding activity of the VCC toxin. We first probed the monosaccharide-binding activity of VCC and demonstrated that the toxin exhibits millimolar affinity for aldohexoses. To understand this specificity, we solved the crystal structure of the VCC beta-prism domain bound to methyl-alpha-mannose. Next, we utilized a mammalian glycan screen to determine that the beta-prism domain preferentially binds complex N-glycans with a heptasaccharide GlcNAc(4)Man(3) core (NGA2). Fluorescence anisotropy and surface plasmon resonance indicated an approximately 100-nM affinity of the beta-prism domain for the heptasaccharide core. Our results suggest that carbohydrate-binding domains on the VCC toxin facilitate high-affinity targeting of mammalian cell membranes, which may contribute to the ability of VCC to lyse cells at picomolar concentrations.
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| - | Vibrio cholerae Cytolysin Recognizes the Heptasaccharide Core of Complex N-Glycans with Nanomolar Affinity.,Levan S, De S, Olson R J Mol Biol. 2012 Dec 28. pii: S0022-2836(12)00949-7. doi:, 10.1016/j.jmb.2012.12.016. PMID:23274141<ref>PMID:23274141</ref>
| + | ==See Also== |
| - | | + | *[[Cytolysin 3D structures|Cytolysin 3D structures]] |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
| + | |
| - | <div class="pdbe-citations 4gx7" style="background-color:#fffaf0;"></div>
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| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Levan, S]] | + | [[Category: Large Structures]] |
| - | [[Category: Olson, R]] | + | [[Category: Levan S]] |
| - | [[Category: Beta-prism]] | + | [[Category: Olson R]] |
| - | [[Category: Carbohydrate-binding domain]]
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| - | [[Category: Cytolysin]]
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| - | [[Category: Glycan-binding]]
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| - | [[Category: Hemolysin]]
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| - | [[Category: Lectin]]
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| - | [[Category: Pore-forming toxin]]
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| - | [[Category: Toxin]]
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