Possani L D, Merino E, Corona M, Bolivar F, Becerril B
Institute of Biotechnology, National Autonomous University of Mexico, Avenida Universidad, 2001, Apartado Postal 510-3, 62210, Cuernavaca, Mexico.
Biochimie. 2000 Sep-Oct;82(9-10):861-8. doi: 10.1016/s0300-9084(00)01167-6.
Most scorpion toxins are ligand peptides that recognize and bind to integral membrane proteins known as ion-channels. To date there are at least 202 distinct sequences described, obtained from 30 different species of scorpions, 27 from the family Buthidae and three from the family Scorpionidae. Toxins that recognize potassium and chloride channels are usually from 29 to 41 amino acids long, stabilized by three or four disulfide bridges, whereas those that recognize sodium channels are longer, 60 to 76 amino acid residues, compacted by four disulfide bridges. Toxins specific for calcium channels are scarcely known and have variable amino acid lengths. The entire repertoire of toxins, independently of their specificity, was analyzed together by computational programs and a phylogenetic tree was built showing two separate branches. The K(+) and Cl(-) channel specific toxins are clustered into 14 subfamilies, whereas those of Na(+) and Ca(2+) specific toxins comprise at least 12 subfamilies. There are clear similarities among them, both in terms of primary sequence and the main three-dimensional folding pattern. A dense core formed by a short alpha helix segment and several antiparallel beta-sheet stretches, maintained by disulfide pairing, seems to be a common structural feature present in all toxins. The physiological function of these peptides is manifested by a blockage of ion passage through the channels or by a modification of the gating mechanism that controls opening and closing of the ion pore.
大多数蝎毒素是配体肽,它们能识别并结合被称为离子通道的整合膜蛋白。迄今为止,已描述了至少202种不同的序列,这些序列来自30种不同的蝎子,其中27种来自钳蝎科,3种来自蝎科。识别钾通道和氯通道的毒素通常由29至41个氨基酸组成,通过三个或四个二硫键稳定,而识别钠通道的毒素则更长,有60至76个氨基酸残基,由四个二硫键紧密排列。对钙通道具有特异性的毒素鲜为人知,且氨基酸长度各不相同。通过计算程序对所有毒素进行了综合分析,无论其特异性如何,并构建了系统发育树,显示出两个独立的分支。钾离子和氯离子通道特异性毒素被聚类为14个亚家族,而钠离子和钙离子特异性毒素至少包括12个亚家族。它们在一级序列和主要三维折叠模式方面都有明显的相似之处。由短α螺旋段和几个反平行β折叠伸展形成的致密核心,通过二硫键配对得以维持,似乎是所有毒素中都存在的一个共同结构特征。这些肽的生理功能表现为阻断离子通过通道,或改变控制离子孔开闭的门控机制。