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To clarify the basis of this synergism we examined the mutual effects of alpha and beta toxin representatives in radio\u2010ligand binding assays. We found positive allosteric interactions between receptor site\u20104 of the excitatory Bj\u2010xtrIT and the depressant LqhIT2 beta toxins and receptor site\u20103 of the alpha toxin Lqh\u03b1IT, on locust neuronal membranes. Unexpectedly, a nontoxic mutant Bj\u2010xtrIT\u2010E15R, which binds with high affinity to receptor site\u20104, was able to enhance Lqh\u03b1IT binding and toxicity similarly to the unmodified Bj\u2010xtrIT. This result indicates that mere binding of a nontoxic ligand to receptor site\u20104 (\u201csilent binding\u201d) induces a conformational change that does not alter channel gating, but influences toxin binding at receptor site\u20103 leading to enhanced toxicity. This finding suggests a new functional role for weakly toxic polypeptides in that they enhance the effect of other active neurotoxins in the arthropod venom. Such silent binding may have also valuable implications in attempts to improve drug efficacy by combining potent drugs with nonactive allosteric enhancers.\u2014Cohen, L., Lipstein, N., Gordon, D. Allosteric interactions between scorpion toxin receptor sites on voltage\u2010gated Na channels imply a novel role for weakly active components in arthropod venom.\n                    <jats:italic>FASEB J<\/jats:italic>\n                    . 20, E1360\u2010E1367 (2006)\n                  <\/jats:p>","DOI":"10.1096\/fj.05-5545fje","type":"journal-article","created":{"date-parts":[[2006,7,29]],"date-time":"2006-07-29T00:57:35Z","timestamp":1154134655000},"page":"1933-1935","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Allosteric interactions between scorpion toxin receptor sites on voltage\u2010gated Na channels imply a novel role for weakly active components in arthropod venom"],"prefix":"10.1096","volume":"20","author":[{"given":"Lior","family":"Cohen","sequence":"first","affiliation":[{"name":"Department of Plant Sciences George S. 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