Structural implications on the interaction of scorpion α-like toxins with the sodium channel receptor site inferred from toxin iodination and pH-dependent binding

Nicolas Gilles, Isabelle Krimm, Francoise Bouet, Oren Froy, Michael Gurevitz, Jean Marc Lancelin, Dalia Gordon*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

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 (LqhαlT), 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 LqhαlT ~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 LqhαlT to this site. In turn, the aromatic ring of Tyr21 takes part in the bioactivity of LqhαlT 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.

Original languageAmerican English
Pages (from-to)1735-1745
Number of pages11
JournalJournal of Neurochemistry
Volume75
Issue number4
DOIs
StatePublished - 2000
Externally publishedYes

Keywords

  • Cockroach
  • Insect sodium channel
  • Locust
  • Scorpion toxin
  • Toxin iodination
  • pH-dependent binding

Fingerprint

Dive into the research topics of 'Structural implications on the interaction of scorpion α-like toxins with the sodium channel receptor site inferred from toxin iodination and pH-dependent binding'. Together they form a unique fingerprint.

Cite this