6ov2: Difference between revisions
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<StructureSection load='6ov2' size='340' side='right'caption='[[6ov2]], [[Resolution|resolution]] 3.20Å' scene=''> | <StructureSection load='6ov2' size='340' side='right'caption='[[6ov2]], [[Resolution|resolution]] 3.20Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6ov2]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[6ov2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridium_perfringens Clostridium perfringens] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. 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 [https://proteopedia.org/fgij/fg.htm?mol=6OV2 FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.2Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | |||
<tr id=' | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6ov2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ov2 OCA], [https://pdbe.org/6ov2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ov2 RCSB], [https://www.ebi.ac.uk/pdbsum/6ov2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ov2 ProSAT]</span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://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> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Clostridium perfringens]] | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Stroud | [[Category: Stroud RM]] | ||
[[Category: Vecchio | [[Category: Vecchio AJ]] | ||
Revision as of 10:17, 11 October 2023
Crystal structure of human claudin-9 in complex with Clostridium perfringens entertoxin C-terminal domain in closed formCrystal structure of human claudin-9 in complex with Clostridium perfringens entertoxin C-terminal domain in closed form
Structural highlights
FunctionCLD9_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.[1] [2] Publication Abstract from PubMedThe 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[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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