CHARACTERIZATION OF A NEW FAMILY OF TOXIN-LIKE PEPTIDES FROM THE VENOM OF THE SCORPION LEIURUS-QUINQUESTRIATUS-HEBRAEUS - H-1-NMR STRUCTUREOF LEIUROPEPTIDE-II

To extend our knowledge about the structural features of short scorpio n toxins, the ion-exchange fractions obtained from Leiurus quinquestri atus hebraeus venom were investigated by plasma desorption mass spectr ometry in order to select low molecular mass polypeptides. Three toxin -like peptides with molecular mass close to 3 kDa, named leiuropeptide s I, II and III, were purified and found devoid of any significant tox icity against mammals and insects. Their amino acid sequences revealed a cysteine pattern analogous to that of short-chain scorpion toxins. The solution structure of leiuropeptide II was determined by 2D H-1-NM R spectroscopy and indicated the presence of a helix accomodating a pr oline, connected to a two-stranded beta-sheet by three disulfide bonds . The overall fold of leiuropeptide II is found to be similar to that of leiurotoxin I, a 31-residue toxin present in the same scorpion veno m which acts on K+ channels. In order to rationalize the absence of to xicity, the electrostatic potential of leiuropeptide II was compared t o that of leiurotoxin I. The peptide is characterized by a large negat ive zone around Glu4, Asp5 and Asp8 residues, beginning in the neighbo urhood of the beta-turn and extending along the helix. In the same are a, leiurotoxin I exhibits a positive surface, around Arg6 and Arg13 ba sic residues, which are essential for its receptor affinity. (C) Munks gaard 1997.