Solution structure of P01, a natural scorpion peptide structurally analogous to scorpion toxins specific for apamin-sensitive potassium channel

✍ Scribed by Blanc, E.; Fremont, V.; Sizun, P.; Meunier, S.; Van Rietschoten, J.; Thevand, A.; Bernassau, J.-M.; Darbon, H.

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 832 KB
• Volume: 24
• Category: Article
• ISSN: 0887-3585
• DOI: 10.1002/(sici)1097-0134(199603)24:3<359::aid-prot9>3.0.co;2-b

✦ Synopsis

The venom of the North African scorpion Androctonus mauretanicus mauretanicus possesses numerous highly active neurotoxins that specifically bind to various ion channels. One of these, P05, has been found to bind specifically to calcium-activated potassium channels and also to compete with apamin, a toxin extracted from bee venom. Besides the highly potent ones, several of these peptides (including that of Pol) have been purified and been found to possess only a very weak, although significant, activity in competition with apamin. The amino acid sequence of PO1 shows that it is shorter than PO5 by two residues. This deletion occurs within an a-helix stretch (residues 5-12). This a-helix has been shown to be involved in the interaction of PO5 with its receptor via two arginine residues. These two arginines are absent in the P O 1 se- quence. Furthermore, a proline residue in position 7 of the PO1 sequence may act as an a-helix breaker. We have determined the solution structure of PO1 by conventional two-dimensional 'H nuclear magnetic resonance and show that 1) the proline residue does not disturb the a-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 structure is conserved, i.e., an a-helix running from residues 5 to 12, two antiparallel stretches of P-sheet (residues 15-20 and 23-27) connected by a type I' p-turn, and three disulfide bridges connecting the a-helix to the P-sheet. o