{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T07:36:09Z","timestamp":1789803369768,"version":"4.0.1"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"24","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1989,12]]},"abstract":"<jats:p>Site-directed and monoclonal antibodies recognizing different extracellular regions of the RII sodium channel alpha subunit have been used to determine the sequences that comprise the receptor for alpha-scorpion toxins by evaluating the effect of antibody on voltage-dependent binding of radio-labeled toxin isolated from Leiurus quinquestriatus to both reconstituted rat brain sodium channel and rat brain synaptosomes. Of six antibodies tested, two recognizing amino acid residues 355-371 and 382-400 located on an extracellular loop between transmembrane segments S5 and S6 of domain I and one recognizing residues 1686-1703 of a similar loop of domain IV inhibit binding by 30-55%. Inhibition is concentration-(EC50 = 0.4-2 microM) and time- (t1\/2 = 40-80 min) dependent. Five different monoclonal antibodies recognizing the same extracellular loop in domain I inhibit binding completely with similar EC50 values as observed for site-directed antibodies. Kinetic studies of the antibody effect are consistent with a slowly reversible competition for the toxin receptor site. Our results suggest that the extracellular loops between segments S5 and S6 of domains I and IV comprise at least part of the alpha-scorpion toxin receptor site and support the membrane topology models in which domains I and IV are adjacent in the tertiary structure of the channel protein and six transmembrane sequences are contained in each of the four homologous domains.<\/jats:p>","DOI":"10.1073\/pnas.86.24.10161","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T07:10:20Z","timestamp":1149059420000},"page":"10161-10165","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":125,"title":["Localization of the receptor site for alpha-scorpion toxins by antibody mapping: implications for sodium channel topology."],"prefix":"10.1073","volume":"86","author":[{"given":"W J","family":"Thomsen","sequence":"first","affiliation":[{"name":"Department of Pharmacology, School of Medicine, University of Washington, Seattle 98195."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W A","family":"Catterall","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, University of Washington, Seattle 98195."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1989,12]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.86.24.10161","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T12:58:57Z","timestamp":1649854737000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.86.24.10161"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1989,12]]},"references-count":0,"journal-issue":{"issue":"24","published-print":{"date-parts":[[1989,12]]}},"alternative-id":["10.1073\/pnas.86.24.10161"],"URL":"https:\/\/doi.org\/10.1073\/pnas.86.24.10161","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1989,12]]},"assertion":[{"value":"1989-12-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}