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

Abstract

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.

Anti‐Insect Toxin 5 (Aalts) from Androctonus Australis

“…Even if lepidopterous larvae had been used for bioassay, lower-resolution chromatography steps would have resulted in small amounts of AaIT5 be- AaITS were manually aligned by creating several gaps to give overall maximum similarity. Amino acid sequences of insect toxins AaIT (Darbon et al, 1982), AaITl and AaIT2 (Loret et al, 1990), AaIT3 (Bougis et al, 1989), AaIT4 (Loret et al, 1991) were published previously.…”

“…4), even though the similarity in the Needleman and Wunsch (1970) algorithm is not as high (38%) as calculated with the depressant toxins (see Results). Scorpion toxins are classified into six groups by taking into account sequence similarities, and AaIT4 belongs to the same group as LqqIT2, LqhIT2 and BjIT2 (Loret et al, 1991). Disulfide bridges, which serve to retain the basic three-dimensional structure, are in constant positions in all known mammal toxins (Darbon et al, 1982;Fontecilla-Camps et al, 1989) and depressant insect toxins, whereas AaIT other than AaIT4 have a shift in one disulfide bond (Fig.…”

κ-Hefutoxin1, a Novel Toxin from the ScorpionHeterometrus fulvipes with Unique Structure and Function

“…1 The lyophilized crude venom was applied on to a Superdex 30 Hiload (16/60) column equilibrated with 50 mM Tris buffer, pH 7.5. Proteins eluted were monitored at 280 nm.…”

“…Scorpions, the largest arachnids, are among the oldest (more than 450 million years) living groups of animals (1). There are ϳ1500 distinct species of scorpions around the world, and their venoms are rich sources of toxins that affect the ion channel functions of excitable and nonexcitable cells (2)(3)(4).…”

1H‐NMR‐Derived Secondary Structure and the Overall Fold of the Potent Anti‐Mammal and Anti‐Insect Toxin III from the Scorpion Leiurus quinquestriatus quinquestriatus

“…Toxins potent towards both mammals and insects have been described in the past few years such as toxin VII (De Lima et al, 1986) from the scorpion Tityus serrulatus and toxin IT4 (Loret et al, 1991) Darbon et al, 1991). Hector, but three-dimensional structures are not available.…”