Peptides and genes coding for scorpion toxins that affect ion-channels

Most scorpion toxins are ligand peptides that recognize and bind to integra l membrane proteins known as ion-channels. To date there are at least 202 d istinct sequences described, obtained from 30 different species of scorpion s, 27 from the family Buthidae and three from the family Scorpionidae. Toxi ns that recognize potassium and chloride channels are usually from 29 to 41 amino acids long, stabilized by three or four disulfide bridges, whereas t hose that recognize sodium channels are longer, 60 to 76 amino acid residue s, compacted by four disulfide bridges. Toxins specific for calcium channel s are scarcely known and have variable amino acid lengths. The entire reper toire of toxins, independently of their specificity, was analyzed together by computational programs and a phylogenetic tree was built showing two sep arate branches. The K+ and Cl- channel specific toxins are clustered into 1 4 subfamilies, whereas those of Na+ and Ca+ specific toxins comprise at lea st 12 subfamilies. There are clear similarities among them, both in terms o f primary sequence and the main three-dimensional folding pattern. A dense core formed by a short alpha helix segment and several antiparallel beta-sh eet stretches, maintained by disulfide pairing, seems to be a common struct ural feature present in all toxins. The physiological function of these pep tides is manifested by a blockage of ion passage through the channels or by a modification of the gating mechanism that controls opening and closing o f the ion pore. (C) 2000 Societe francaise de biochimie et biologie molecul aire / Editions scientifiques et medicales Elsevier SAS.