View source for 6ov3


==Crystal structure of human claudin-9 in complex with Clostridium perfringens entertoxin C-terminal domain in open form==
<StructureSection load='6ov3' size='340' side='right'caption='[[6ov3]], [[Resolution|resolution]] 3.25&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6ov3]] 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=6OV3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6OV3 FirstGlance]. <br>
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6ov2|6ov2]]</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=6ov3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ov3 OCA], [http://pdbe.org/6ov3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ov3 RCSB], [http://www.ebi.ac.uk/pdbsum/6ov3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ov3 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. 
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== 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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
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</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]]