SOLUTION STRUCTURE OF P01, A NATURAL SCORPION PEPTIDE STRUCTURALLY ANALOGOUS TO SCORPION TOXINS SPECIFIC FOR APAMIN-SENSITIVE POTASSIUM CHANNEL

The venom of the North African scorpion Androctonus mauretanicus maure tanicus possesses numerous highly active neurotoxins that specifically bind to various ion channels, One of these, P05, has been found to bi nd specifically to calcium-activated potassium channels and also to co mpete with apamin, a toxin extracted from bee venom. Besides the highl y potent ones, several of these peptides (including that of P01) have been purified and been found to possess only a very weak, although sig nificant, activity in competition with apamin. The amino acid sequence of P01 shows that it is shorter than P05 by two residues, This deleti on occurs within an alpha-helix stretch (residues 5-12). This alpha-he lix has been shown to be involved in the interaction of P05 with its r eceptor via two arginine residues, These two arginines are absent in t he P01 sequence, Furthermore, a proline residue in position 7 of the P 01 sequence may act as an alpha-helix breaker. We have determined the solution structure of P01 by conventional two-dimensional H-1 nuclear magnetic resonance and show that 1) the proline residue does not distu rb the alpha-helix running from residues 5 to 12; 2) the two arginines are topologically replaced by two acidic residues, which explains the drop in activity; 3) the residual binding activity may be due to the histidine residue in position 9; and 4) the overall secondary structur e is conserved, i.e., an alpha-helix running from residues 5 to 12, tw o antiparallel stretches of beta-sheet (residues 15-20 and 23-27) conn ected by a type I' beta-turn, and three disulfide bridges connecting t he alpha-helix to the beta-sheet. (C) 1996 Wiley-Liss, Inc.