{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T16:17:54Z","timestamp":1790871474239,"version":"4.1.0"},"reference-count":0,"publisher":"Portland Press Ltd.","issue":"1","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2003,11,15]]},"abstract":"<jats:p>Rhodocetin is a snake venom protein that binds to \u03b12\u03b21 integrin, inhibiting its interaction with its endogenous ligand collagen. We have determined the mechanism by which rhodocetin inhibits the function of \u03b12\u03b21. The interaction of \u03b12\u03b21 with collagen and rhodocetin differed: Ca2+ ions and slightly acidic pH values increased the binding of \u03b12\u03b21 integrin to rhodocetin in contrast with their attenuating effect on collagen binding, suggesting that rhodocetin preferentially binds to a less active conformation of \u03b12\u03b21 integrin. The \u03b12A-domain [von Willebrand factor domain A homology domain (A-domain) of the integrin \u03b12 subunit] is the major site for collagen binding to \u03b12\u03b21. Recombinant \u03b12A-domain bound rhodocetin, demonstrating that the A-domain is also the rhodocetin-binding domain. Although the interaction of \u03b12\u03b21 with rhodocetin is affected by altering divalent cations, the interaction of the A-domain was divalent-cation-independent. The rhodocetin-binding site on the \u03b12A-domain was mapped first by identifying an anti-\u03b12 antibody that blocked rhodocetin binding and then mapping the epitope of the antibody using human\u2013mouse \u03b12A-domain chimaeras; and secondly, by binding studies with \u03b12A-domain, which bear point mutations in the vicinity of the mapped epitope. In this way, the rhodocetin-binding site was identified as the \u03b13\u2013\u03b14 loop plus adjacent \u03b1-helices. This region is known to form part of the collagen-binding site, thus attaining a mainly competitive mode of inhibition by rhodocetin.<\/jats:p>","DOI":"10.1042\/bj20030373","type":"journal-article","created":{"date-parts":[[2003,11,11]],"date-time":"2003-11-11T15:45:26Z","timestamp":1068565526000},"page":"77-85","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["The \u03b12\u03b21 integrin inhibitor rhodocetin binds to the A-domain of the integrin \u03b12 subunit proximal to the collagen-binding site"],"prefix":"10.1042","volume":"376","author":[{"given":"Johannes A.","family":"EBLE","sequence":"first","affiliation":[{"name":"Institute of Physiological Chemistry and Pathobiochemistry, M\u00fcnster University Hospital, Waldeyerstr. 15, 48149 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danny S.","family":"TUCKWELL","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, University of Manchester, Stopford Building, Oxford Rd, Manchester, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","container-title":["Biochemical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/376\/1\/77\/712383\/bj3760077.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/376\/1\/77\/712383\/bj3760077.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,22]],"date-time":"2021-11-22T14:45:35Z","timestamp":1637592335000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/biochemj\/article\/376\/1\/77\/43942\/The-2-1-integrin-inhibitor-rhodocetin-binds-to-the"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,11,15]]},"references-count":0,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2003,11,15]]}},"URL":"https:\/\/doi.org\/10.1042\/bj20030373","relation":{},"ISSN":["0264-6021","1470-8728"],"issn-type":[{"value":"0264-6021","type":"print"},{"value":"1470-8728","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,11,15]]}}}