Teichert Russell W, Jimenez Elsie C, Olivera Baldomero M
Department of Biology, University of Utah, Salt Lake City, Utah 84112, USA.
Biochemistry. 2005 May 31;44(21):7897-902. doi: 10.1021/bi047274+.
We report the purification and characterization of a new conotoxin from the venom of Conus radiatus. The peptide, alphaS-conotoxin RVIIIA (alphaS-RVIIIA), is biochemically unique with respect to its amino acid sequence, post-translational modification, and molecular targets. In comparison to other nicotinic antagonists from Conus venoms, alphaS-RVIIIA exhibits an unusually broad targeting specificity for nicotinic acetylcholine receptor (nAChR) subtypes, as assayed by electrophysiology. The toxin is paralytic to mice and fish, consistent with its nearly irreversible block of the neuromuscular nAChR. Similar to other antagonists of certain neuronal nAChRs, the toxin also elicits seizures in mice upon intracranial injection. The only previously characterized conotoxin from the S superfamily, sigma-conotoxin GVIIIA, is a specific competitive antagonist of the 5-HT3 receptor; thus, alphaS-RVIIIA defines a novel family of nicotinic antagonists within the S superfamily. All previously characterized competitive conotoxin nAChR antagonists have been members of the A superfamily of conotoxins. Our working hypothesis is that the particular group of fish-hunting Conus species that includes Conus radiatus uses the alphaS-conotoxin family to target the muscle nAChR and paralyze prey.
我们报告了从辐射芋螺毒液中纯化和鉴定一种新的芋螺毒素的过程。该肽，αS-芋螺毒素RVIIIA（αS-RVIIIA），在氨基酸序列、翻译后修饰和分子靶点方面具有生物化学独特性。与来自芋螺毒液的其他烟碱拮抗剂相比，通过电生理学测定，αS-RVIIIA对烟碱型乙酰胆碱受体（nAChR）亚型表现出异常广泛的靶向特异性。该毒素对小鼠和鱼类具有麻痹作用，这与其对神经肌肉nAChR的几乎不可逆阻断一致。与某些神经元nAChR的其他拮抗剂类似，该毒素在颅内注射后也会引发小鼠癫痫发作。之前唯一被鉴定的来自S超家族的芋螺毒素，σ-芋螺毒素GVIIIA，是5-HT3受体的特异性竞争性拮抗剂；因此，αS-RVIIIA定义了S超家族内一个新的烟碱拮抗剂家族。所有之前被鉴定的竞争性芋螺毒素nAChR拮抗剂都是芋螺毒素A超家族的成员。我们的工作假设是，包括辐射芋螺在内的特定一组以鱼为食的芋螺物种利用αS-芋螺毒素家族靶向肌肉nAChR并麻痹猎物。
