An anti-insect toxin purified from the scorpion Androctonus australis Hector also acts on the alpha- and beta-sites of the mammalian sodium channel: sequence and circular dichroism study.
A new anti-insect neurotoxin, AaH IT4, has been isolated from the venom of the North African scorpion Androctonus australis Hector. This polypeptide has a toxic effect on insects and mammals and is capable of competing with anti-insect scorpion toxins for binding to the sodium channel of insects; it also modulates the binding of alpha-type and beta-type anti-mammal scorpion toxins to the mammal sodium channel. This is the first report of a scorpion toxin able to exhibit these three kinds of activity. The molecule is composed of 65 amino acid residues and lacks methionine and, more unexpectedly, proline, which until now has been considered to play a role in the folded structure of all scorpion neurotoxins. The primary structure showed a poor homology with the sequences of other scorpion toxins; however, it had features in common with beta-type toxins. In fact, radioimmunoassays using antibodies directed to scorpion toxins representative of the main structural groups showed that there is a recognition of AaH IT4 via anti-beta-type toxin antibodies only. A circular dichroism study revealed a low content of regular secondary structures, particularly in beta-sheet structures, when compared to other scorpion toxins. This protein might be the first member of a new class of toxins to have ancestral structural features and a wide toxic range.
Loret
E P
EP
Laboratoire de Biochimie, CNRS URA 1179, Faculté de Médecine, Secteur Nord, Marseille, France.
Martin-Eauclaire
M F
MF
Mansuelle
P
P
Sampieri
F
F
Granier
C
C
Rochat
H
H
D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D002942:Circular Dichroism; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000737:chemistry*; D009498:Neurotoxins / Q000737:chemistry*; D011487:Protein Conformation; D012604:Scorpion Venoms / Q000737:chemistry*; D012605:Scorpions / Q000032:analysis*; D015222:Sodium Channels / Q000737:chemistry*
D009479:Neuropeptides; D009498:Neurotoxins; D012604:Scorpion Venoms; D015222:Sodium Channels; C066911:scorpion toxin AaH IT4