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6ov2
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of human claudin-9 in complex with Clostridium perfringens entertoxin C-terminal domain in closed form== | |
| + | <StructureSection load='6ov2' size='340' side='right'caption='[[6ov2]], [[Resolution|resolution]] 3.20Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6ov2]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_perfringens"_veillon_and_zuber_1898 "bacillus perfringens" veillon and zuber 1898] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OV2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6OV2 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6ov3|6ov3]]</td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CLDN9 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), cpe ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1502 "Bacillus perfringens" Veillon and Zuber 1898])</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=6ov2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ov2 OCA], [http://pdbe.org/6ov2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ov2 RCSB], [http://www.ebi.ac.uk/pdbsum/6ov2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ov2 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/CLD9_HUMAN CLD9_HUMAN]] Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity. (Microbial infection) Acts as a receptor for hepatitis C virus (HCV) entry into hepatic cells.<ref>PMID:17804490</ref> <ref>PMID:20375010</ref> [[http://www.uniprot.org/uniprot/ELTB_CLOPF ELTB_CLOPF]] This enterotoxin is responsible for many cases of a mild type of food poisoning. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The human pathogenic bacterium Clostridium perfringens secretes an enterotoxin (CpE) that targets claudins through its C-terminal receptor-binding domain (cCpE). Isoform-specific binding by CpE causes dissociation of claudins and tight junctions (TJs), resulting in cytotoxicity and breakdown of the gut epithelial barrier. Here, we present crystal structures of human claudin-9 (hCLDN-9) in complex with cCpE at 3.2 and 3.3 A. We show that hCLDN-9 is a high-affinity CpE receptor and that hCLDN-9-expressing cells undergo cell death when treated with CpE but not cCpE, which lacks its cytotoxic domain. Structures reveal cCpE-induced alterations to 2 epitopes known to enable claudin self-assembly and expose high-affinity interactions between hCLDN-9 and cCpE that explain isoform-specific recognition. These findings elucidate the molecular bases for hCLDN-9 selective ion permeability and binding by CpE, and provide mechanisms for how CpE disrupts gut homeostasis by dissociating claudins and TJs to affect epithelial adhesion and intercellular transport. | ||
| - | + | Claudin-9 structures reveal mechanism for toxin-induced gut barrier breakdown.,Vecchio AJ, Stroud RM Proc Natl Acad Sci U S A. 2019 Sep 3;116(36):17817-17824. doi:, 10.1073/pnas.1908929116. Epub 2019 Aug 21. PMID:31434788<ref>PMID:31434788</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6ov2" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Bacillus perfringens veillon and zuber 1898]] | ||
| + | [[Category: Human]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Stroud, R M]] | ||
| + | [[Category: Vecchio, A J]] | ||
| + | [[Category: Cell adhesion]] | ||
| + | [[Category: Claudin]] | ||
| + | [[Category: Enterotoxin]] | ||
| + | [[Category: Tight junction protein]] | ||
| + | [[Category: Transmembrane protein]] | ||
Revision as of 11:57, 1 January 2020
Crystal structure of human claudin-9 in complex with Clostridium perfringens entertoxin C-terminal domain in closed form
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