关键词: 蝎神经毒素是存在于蝎尾毒液中的一组活性蛋白/多肽, 可概分为长链毒素和短链毒素. 长链毒素由60~80个氨基酸组成, 包括4对二硫键, 主要作用于电位依赖的钠离子通道, 短链毒素一般由30~40个氨基酸和2~4 对二硫键组成, 专一地作用于K⁺, Cl^-等离子通道. 长链神经毒素具有不同的种属专一性, 可分为哺乳动物神经毒素、昆虫神经毒素甲壳动物神经毒素.

Abstract:

Three bioactivity variant neurotoxins, BmK M1, M4 and M8, have been purified from venom of the Chinese scorpion Buthus martensii Karsch. They possess distinct toxic activity on mice in vivo with different electrostatic properties. The relative toxicities of BmK M1, M4 and M8 are 13.3:2.5:1, which interestingly correspond to their respective pI values, ranging from basic to acidic, of 9.01, 7.53 and 5.30. In addition, the BmK M1 and M4 belong to α like toxin, while the BmK M8 belongs to classical α toxin so that they may bind to Na ₊ channel at different microsite. The crystal structures of BmK M1, M4 have been determined and refined at resolutions 0.17 nm (M1), 0.13 nm (M4), respectively. The structure investigations in association with the site mutagenesis experiments revealed three significant surface areas: Face A and B relevant to the toxic potency expression; Site RC involved in the receptor binding specificity. Interestingly the substitutions with negative charge potentid residues in the Face B will dramatically reduce the toxic activity of the molecule, which suggested a "Charge potential mediated mechanism" for toxicity expression. Based on the high resolution structure, the most interesting finding is a unusual non prolyl cis peptide bond (residue 9～10) appeared in the site relative to receptor binding of the α like toxin BmK M1 and M4, but not in the classical α toxin BmK M8. The observations provide a possible structural basis for the α like toxin receptor binding site selectivity and propose a " cis peptide bond mediated mechanism" for the toxin receptor binding specificity. This manifested a way to achieve high levels of molecular specificity through the strained backbone geometry.

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