{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T07:35:16Z","timestamp":1789803316461,"version":"4.0.1"},"reference-count":24,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2004,4,1]],"date-time":"2004-04-01T00:00:00Z","timestamp":1080777600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2004,4]]},"abstract":"<jats:p>\n                    Gating modifiers constitute a large group of polypeptide toxins that interact with the voltage\u2010sensing module of ion channels. Among them, scorpion \u03b2\u2010toxins induce a negative shift in the voltage dependence of sodium channel activation. To explain their effect, a \u201cvoltage sensor trapping\u201d model has been proposed in which the voltage sensor of domain\u2010II (DIIS4) is trapped in an outward, activated position by a prebound \u03b2\u2010toxin upon membrane depolarization. Whereas toxin effect on channel activation was enhanced upon neutralization of the two outermost arginines in DIIS4, toxin residues involved in sensor trapping have not been identified. Using the scorpion excitatory \u03b2\u2010toxin, Bj\u2010xtrIT, we found two conserved acidic residues, Glu15 and Glu30, mandatory for toxin action. Whereas mutagenesis of Glu30 affected both toxicity and binding affinity, substitutions E15A\/F abolished activity but had minor effects on binding. Complete uncoupling of activity from binding was obtained with mutant E15R, acting as an efficient antagonist of Bj\u2010xtrIT. On the basis of the voltage sensor trapping model and our results, we propose that Glu15 interacts with the emerging gating charges of DIIS4 upon membrane depolarization. Conserved acidic residues found in a variety of gating modifiers from scorpions and spiders may interact similarly with the voltage sensor.\u2014 Izhar, K., Lior, C., Nicolas, G., Dalia, G., Michael, G. Conversion of a scorpion toxin agonist into an antagonist highlights an acidic residue involved in voltage sensor trapping during activation of neuronal Na\n                    <jats:sup>+<\/jats:sup>\n                    channels.\n                  <\/jats:p>","DOI":"10.1096\/fj.03-0733com","type":"journal-article","created":{"date-parts":[[2004,3,30]],"date-time":"2004-03-30T18:23:01Z","timestamp":1080670981000},"page":"683-689","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Conversion of a scorpion toxin agonist into an antagonist highlights an acidic residue involved in voltage sensor trapping during activation of neuronal Na\n                    <sup>+<\/sup>\n                    channels"],"prefix":"10.1096","volume":"18","author":[{"given":"Karbat","family":"Izhar","sequence":"first","affiliation":[{"name":"Department of Plant Sciences, George S. 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