Characterization of toxin III of the scorpion Leiurus quinquestriatus quinquestriatus: A new type of alpha‐toxin highly toxic both to mammals and insects

Publisher Website
Google Scholar
Abstract
The primary structure of toxin III of Leiurus quinquestriatus quinquestriatus (Lqq III) was elucidated by automatic Edman degradation of the reduced and S‐carboxymethylated protein and derived tryptic peptides. Like other scorpion toxins that are active on sodium channels, Lqq III, consisting of 64 amino acids, is a 7 kDa single‐chain polypeptide crosslinked by four disulfide bridges. It belongs to the α‐toxin group, as judged by competition experiments with 125I AaH II for binding to rat brain synaptosomes (Ko.5 = 7 × 10‐−7 M). Lqq III is the first α‐toxin to be characterized that is highly toxic to mice [LD50 = μG (7.1 nmol)/kg body wt], by subcutaneous injection, insects Blatella germanica [LD50 = 60 ng (8.5 pmol)/g body wt.] and Musca domestica [LD50 = 120 ng (17 pmol)/g body wt]. When tested via the intracerebroventricular route, the toxicity for mice [55 μg (8 nmol)/kg] was of the same order as that found by subcutaneous injection, indicating that Lqq III has a higher affinity for peripheral sodium channels than for those of the central nervous system. There are three differences between the sequences of Lqq III and LqhαlT, an α‐toxin isolated from the venom of Leiurvs quinquestriatus hebraeus. These substitutions are found at positions 20,24, and 64 (Ser‐→Ala, Asp‐→Glu and His‐→Arg, respectively). Surprisingly LqhαlT is only weakly active in mice [LD50 = 5 mg (0.7 μmol)/kg], while in insects its toxicity is similar to that of Lqq III [140 ng (20 pmol)/g body wt blowfly larvae]. These observations are relevant to the definition of scorpion toxin structure‐activity relationships.