MAUROTOXIN, A 4 DISULFIDE BRIDGE TOXIN FROM SCORPIO-MAURUS VENOM - PURIFICATION, STRUCTURE AND ACTION ON POTASSIUM CHANNELS

A new toxin acting on K+ channels, maurotoxin (MTX), has been purified to homogeneity from the venom of the chactoid scorpion Scorpio maurus . MTX is a basic single chain 34 amino acid residue polypeptide, amida ted at its C terminal, and crosslinked by four disulfide bridges, It s hows 29-68% sequence identity with other K+ channel toxins, and presen ts an original disulfide pattern, the last two half-cystine residues ( 31-34) being connected, Although the first three disulfide bonds hare not been defined experimentally, modelling based on tile structure of charybdotoxin favored two combinations out of six, one of which has tw o bridges (3-24 and 9-29) in common with the general motif of scorpion toxins, The last bridge would connect residues 13 and 19. MTX inhibit s the binding to Eat brain synaptosomal membranes of both [I-125]apami n, a SKCa channel blocker (IC50 5 nM), and [I-125]kaliotoxin, a Kv cha nnel blocker (IC50 30 pM). MTX blocks the Kv1.1, Kv1.2 and Kv1.3 curre nts expressed in Xenopus oocytes with IC50 of 45, 0.8 and 180 nM, resp ectively, MTX represents a member of a new class of short toxins with 4 disulfide bridges, active on voltage-dependent K+ channel and also c ompeting with apamin for binding to its receptor. (C) 1997 Federation of European Biochemical Societies.