BjαIT: A novel scorpion α-toxin selective for insects - Unique pharmacological tool

Tal Arnon, Tamara Potikha, Daniel Sher, Menashe Elazar, Wenfu Mao, Tzachy Tal, Frank Bosmans, Jan Tytgat, Nissim Ben-Arie, Eliahu Zlotkin

Research output: Contribution to journalArticlepeer-review

Abstract

Long-chain neurotoxins derived from the venom of the Buthidae scorpions, which affect voltage-gated sodium channels (VGSCs) can be subdivided according to their toxicity to insects into insect-selective excitatory and depressant toxins (β-toxins) and the α-like toxins which affect both mammals and insects. In the present study by the aid of reverse-phase HPLC column chromatography, RT-PCR, cloning and various toxicity assays, a new insect selective toxin designated as BjαIT was isolated from the venom of the Judean Black Scorpion (Buthotus judaicus), and its full primary sequence was determined: MNYLVVICFALLLMTVVESGRDAYIADNLNCAYTCGSNSYCNTECTKNGAVSGYCQWLGKYGNACWCINLPDKVPI RIPGACR (leader sequence is underlined). Despite its lack of toxicity to mammals and potent toxicity to insects, BjαIT reveals an amino acid sequence and an inferred spatial arrangement that is characteristic of the well-known scorpion α-toxins highly toxic to mammals. BjαITs sharp distinction between insects and mammals was also revealed by its effect on sodium conductance of two cloned neuronal VGSCs heterloguously expressed in Xenopus laevis oocytes and assayed with the two-electrode voltage-clamp technique. BjαIT completely inhibits the inactivation process of the insect para/tipE VGSC at a concentration of 100 nM, in contrast to the rat brain Na v1.2/β1 which is resistant to the toxin. The above categorical distinction between mammal and insect VGSCs exhibited by BjαIT enables its employment in the clarification of the molecular basis of the animal group specificity of scorpion venom derived neurotoxic polypeptides and voltage-gated sodium channels.

Original languageEnglish (US)
Pages (from-to)187-195
Number of pages9
JournalInsect Biochemistry and Molecular Biology
Volume35
Issue number3
DOIs
StatePublished - Mar 2005

Keywords

  • Alpha neurotoxins
  • Black Judean Scorpion
  • Insect selectivity
  • Scorpion venom
  • Voltage-Gated Sodium Channels

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Insect Science

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