{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T21:57:39Z","timestamp":1788299859795,"version":"build-2803163510"},"reference-count":41,"publisher":"Portland Press Ltd.","issue":"1","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2007,8,15]]},"abstract":"<jats:p>Av3 is a short peptide toxin from the sea anemone Anemonia viridis shown to be active on crustaceans and inactive on mammals. It inhibits inactivation of Navs (voltage-gated Na+ channels) like the structurally dissimilar scorpion \u03b1-toxins and type\u00a0I sea anemone toxins that bind to receptor site-3. To examine the potency and mode of interaction of Av3 with insect Navs, we established a system for its expression, mutagenized it throughout, and analysed it in toxicity, binding and electrophysiological assays. The recombinant Av3 was found to be highly toxic to blowfly larvae (ED50=2.65\u00b10.46\u00a0pmol\/100\u00a0mg), to compete well with the site-3 toxin Lqh\u03b1IT (from the scorpion Leiurus quinquestriatus) on binding to cockroach neuronal membranes (Ki=21.4\u00b17.1\u00a0nM), and to inhibit the inactivation of Drosophila melanogaster channel, DmNav1, but not that of mammalian Navs expressed in Xenopus oocytes. Moreover, like other site-3 toxins, the activity of Av3 was synergically enhanced by ligands of receptor site-4 (e.g. scorpion \u03b2-toxins). The bioactive surface of Av3 was found to consist mainly of aromatic residues and did not resemble any of the bioactive surfaces of other site-3 toxins. These analyses have portrayed a toxin that might interact with receptor site-3 in a different fashion compared with other ligands of this site. This assumption was corroborated by a D1701R mutation in DmNav1, which has been shown to abolish the activity of all other site-3 ligands, except Av3. All in all, the present study provides further evidence for the heterogeneity of receptor site-3, and raises Av3 as a unique model for design of selective anti-insect compounds.<\/jats:p>","DOI":"10.1042\/bj20070233","type":"journal-article","created":{"date-parts":[[2007,11,7]],"date-time":"2007-11-07T15:36:45Z","timestamp":1194449805000},"page":"41-48","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Molecular analysis of the sea anemone toxin Av3 reveals selectivity to insects and demonstrates the heterogeneity of receptor site-3 on voltage-gated Na+ channels"],"prefix":"10.1042","volume":"406","author":[{"given":"Yehu","family":"Moran","sequence":"first","affiliation":[{"name":"Department of Plant Sciences, George S. 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Pharmacol."},{"key":"2021112213322139100_B9","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/S0014-5793(02)03653-0","article-title":"The sea anemone Bunodosoma granulifera contains surprisingly efficacious and potent insect-selective toxins","volume":"532","author":"Bosmans","year":"2002","journal-title":"FEBS Lett."},{"key":"2021112213322139100_B10","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.ibmb.2004.11.005","article-title":"Bj\u03b1IT: a novel scorpion \u03b1-toxin selective for insects: unique pharmacological tool","volume":"35","author":"Arnon","year":"2005","journal-title":"Insect Biochem. Mol. 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Biol. Chem."},{"key":"2021112213322139100_B27","first-page":"493","article-title":"A simple method of estimating fifty-percent endpoint","volume":"27","author":"Reed","year":"1938","journal-title":"Am. J. Hyg."},{"key":"2021112213322139100_B28","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1046\/j.1471-4159.2000.0751735.x","article-title":"Structural implications on the interaction of scorpion \u03b1-like toxins with the sodium channel receptor site inferred from toxin iodination and pH-dependent binding","volume":"75","author":"Gilles","year":"2000","journal-title":"J. Neurochem."},{"key":"2021112213322139100_B29","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1016\/0003-2697(77)90192-0","article-title":"Radioiodination of scorpion and snake neurotoxins","volume":"82","author":"Rochat","year":"1977","journal-title":"Anal. Biochem."},{"key":"2021112213322139100_B30","doi-asserted-by":"crossref","first-page":"4364","DOI":"10.1523\/JNEUROSCI.22-11-04364.2002","article-title":"Domain 2 of Drosophila para voltage-gated sodium channel confers insect properties to a rat brain channel J","volume":"22","author":"Shichor","year":"2002","journal-title":"Neurosci."},{"key":"2021112213322139100_B31","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1085\/jgp.110.2.119","article-title":"Functional expression of Drosophila para sodium channels: modulation by membrane protein TipE and toxin pharmacology","volume":"110","author":"Warmke","year":"1997","journal-title":"J. Gen. Physiol."},{"key":"2021112213322139100_B32","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/BF00585406","article-title":"Anemonia sulcata toxins modify activation and inactivation of Na+ currents in a crayfish neurone","volume":"404","author":"Hartung","year":"1985","journal-title":"Pflugers Arch."},{"key":"2021112213322139100_B33","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/0014-5793(93)81147-R","article-title":"Binding of \u03b1 scorpion toxin to insect sodium channels is not dependent on membrane potential","volume":"315","author":"Gordon","year":"1993","journal-title":"FEBS Lett."},{"key":"2021112213322139100_B34","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1096\/fj.03-0733com","article-title":"Conversion of a scorpion toxin agonist into an antagonist highlights an acidic residue involved in voltage sensor trapping during activation of neuronal Na+ channels","volume":"18","author":"Karbat","year":"2004","journal-title":"FASEB J."},{"key":"2021112213322139100_B35","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1021\/cr000100n","article-title":"Vibrational spectroscopic detection of \u03b2- and \u03b3-turns in synthetic and natural peptides and proteins","volume":"103","author":"Vass","year":"2003","journal-title":"Chem. 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