New toxins acting on sodium channels from the scorpion Leiurus quinquestriatus hebraeus suggest a clue to mammalian vs insect selectivity

• Published in: Toxicon (Oxford) Vol. 36; no. 8; pp. 1141 - 1154
• Main Authors: Sautière, Pierre, Cestèle, Sandrine, Kopeyan, Charles, Martinage, Arlette, Drobecq, Hervé, Doljansky, Yvon, Gordon, Dalia
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.08.1998; Elsevier Science; Elsevier
• Subjects: Amino Acid Sequence; Amino Acids - analysis; Animal poisons toxicology. Antivenoms; Animals; Biological and medical sciences; Buthidae; Cockroaches; Leiurus quinquestriatus hebraeus; Life Sciences; Medical sciences; Mice; Mice, Inbred C57BL; Molecular Sequence Data; Neurotoxins - chemistry; Neurotoxins - toxicity; Rats; Scorpion Venoms - chemistry; Sequence Homology, Amino Acid; Sodium Channels - drug effects; Species Specificity; Synaptosomes - drug effects; Toxicology; Sodium Ions; Scorpionides; Molecular structure; Toxicity; Insecta; Ionic channel; Species specificity; Structure activity relation; Dictyoptera; Aminoacid sequence; Purification; Interspecific comparison; Blattellidae; Rodentia; Animal origin; Blattella germanica; Toxin; Arachnida; Vertebrata; Mammalia; Mouse; Arthropoda; Animal; Venom; Invertebrata; Comparative study
• ISSN: 0041-0101; 1879-3150; 0041-0101
• DOI: 10.1016/S0041-0101(98)00080-4

Two new toxins were purified from Leiurus quinquestriatus hebraeus (Lqh) scorpion venom, Lqh II and Lqh III. Lqh II sequence reveals only two substitutions, as compared to AaH II, the most active scorpion α-toxin on mammals from Androctounus australis Hector. Lqh III shares 80% sequence identity with the α-like toxin Bom III, from Buthus occitanus mardochei. Using bioassays on mice and cockroach coupled with competitive binding studies with 125I-labeled scorpion α-toxins on rat brain and cockroach synaptosomes, the animal selectivity was examined. Lqh II has comparable activity to mammals as AaH II, but reveals significantly higher activity to insects attributed to its C-terminal substitution, and competes at low concentration for binding on both mammalian and cockroach sodium channels. Lqh II thus binds to receptor site 3 on sodium channels. Lqh III is active on both insects and mammals but competes for binding only on cockroach. The latter indicates that Lqh III binds to a distinct receptor site. Thus, Lqh II and Lqh III represent two different scorpion toxin groups, the α- and α-like toxins, respectively, according to the structural and pharmacological criteria. These new toxins may serve as a lead for clarification of the structural basis for insect vs mammal selectivity of scorpion toxins.