Covalent structure of the insect toxin of the North African scorpion Androctonus australis Hector

Abstract

The complete covalent structure of the insect toxin purified from the venom of the North African scorpion A. australis was described. Its amino acid sequence was established by phenylisothiocyanate degradation of several protein derivatives and proteolytic fragments in a liquid protein sequencer using a protein or a peptide program. The position of the 4 disulfide bridges were deduced by analysis of proteolytic peptides before and after performic oxidation, and by partial labeling of Cys residues with [14C]iodoacetic acid and determining the specific radioactivities of the S-[14C]-carboxymethylated phenylthiohydantoin Cys. The sequences of the insect and mammal toxins from scorpions were aligned with homology with the positions of 7 Cys residues as registers. The mammal and insect toxins had 3 disulfide bridges at homologous positions. The 4th bridge was different in that Cys12 in mammal toxin 2 was replaced by Cys38 in the insect toxin. The position of the disulfide bridges was probably the same for all scorpion neurotoxins active on mammals. The shift of 1 Cys residue in the insect toxin may induce a conformational change in the structure of the protein, which may partially account for the total specificity of this toxin for insect nervous system.