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- Title
Structural Implications on the Interaction of Scorpion α-like Toxins with the Sodium Channel Receptor Site Inferred from Toxin Iodination and pH-Dependent Binding.
- Authors
Gilles, Nicolas; Krimm, Isabelle; Bouet, Francoise; Froy, Oren; Gurevitz, Michael; Lancelin, Jean-Marc; Gordon, Dalia
- Abstract
Abstract: The α-like toxin from the venom of the scorpion Leiurus quinquestriatus hebraeus (Lqh III) binds with high affinity to receptor site 3 on insect sodium channels but does not bind to rat brain synaptosomes. The binding affinity of Lqh III to cockroach neuronal membranes was fivefold higher at pH 6.5 than at pH 7.5. This correlated with an increase in the electropositive charge on the toxin surface resulting from protonation of its four histidines. Radioiodination of Tyr14 of Lqh III abolished its binding to locust but not cockroach sodium channels, whereas the noniodinated toxin bound equally well to both neuronal preparations. Radioiodination of Tyr10 or Tyr21 of the structurally similar α-toxin from L. quinquestriatus hebraeus (LqhαIT), as well as their substitution by phenylalanine, had only minor effects on binding to cockroach neuronal membranes. However, substitution of Tyr21, but not Tyr14, by leucine decreased the binding affinity of LqhαIT ∼87-fold. Thus, Tyr14 is involved in the bioactivity of Lqh III to locust receptor site 3 and is not crucial for the binding of LqhαIT to this site. In turn, the aromatic ring of Tyr21 takes part in the bioactivity of LqhαIT to insects. These results highlight subtle architectural variations between locust and cockroach receptor site 3, in addition to previous results demonstrating the competence of Lqh III to differentiate between insect and mammalian sodium channel subtypes.
- Subjects
VENOM; SCORPIONS; SYNAPTOSOMES; SODIUM channels
- Publication
Journal of Neurochemistry, 2000, Vol 75, Issue 4, p1735
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1046/j.1471-4159.2000.0751735.x