6ov2 | pdb_00006ov2

Crystal structure of human claudin-9 in complex with Clostridium perfringens entertoxin C-terminal domain in closed form

spinqualitylabelsall models 6ov2, resolution 3.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6ov2 is a 2 chain structure with sequence from Clostridium perfringens and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.2Å Ligands: GOL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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