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
| العنوان: | 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 |
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| المؤلفون: | Maya Gur, Michael Gurevitz, Dalia Gordon, Lior Cohen, Izhar Karbat, Roy Kahn, Yehu Moran |
| المصدر: | Biochemical Journal. 406:41-48 |
| بيانات النشر: | Portland Press Ltd., 2007. |
| سنة النشر: | 2007 |
| مصطلحات موضوعية: | Models, Molecular, Insecta, Leiurus, Xenopus, Molecular Sequence Data, Cockroaches, Receptors, Cell Surface, Sea anemone, Arginine, medicine.disease_cause, Biochemistry, Sodium Channels, Cnidarian Venoms, Species Specificity, Botany, medicine, Animals, Amino Acid Sequence, Receptor, Molecular Biology, Peptide sequence, Aspartic Acid, biology, Voltage-gated ion channel, Toxin, Circular Dichroism, Cell Biology, biology.organism_classification, Recombinant Proteins, Drosophila melanogaster, Sea Anemones, Amino Acid Substitution, Mutagenesis, Larva, Mutation, Oocytes, Ion Channel Gating, Research Article |
| الوصف: | 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 Na(v)s (voltage-gated Na+ channels) like the structurally dissimilar scorpion alpha-toxins and type I sea anemone toxins that bind to receptor site-3. To examine the potency and mode of interaction of Av3 with insect Na(v)s, 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+/-0.46 pmol/100 mg), to compete well with the site-3 toxin LqhalphaIT (from the scorpion Leiurus quinquestriatus) on binding to cockroach neuronal membranes (K(i)=21.4+/-7.1 nM), and to inhibit the inactivation of Drosophila melanogaster channel, DmNa(v)1, but not that of mammalian Na(v)s 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 beta-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 DmNa(v)1, 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. |
| تدمد: | 1470-8728 0264-6021 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0640d5725808f8a0d812078a734ec735Test https://doi.org/10.1042/bj20070233Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....0640d5725808f8a0d812078a734ec735 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14708728 02646021 |
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