The putative bioactive surface of insect-selective scorpion excitatory neurotoxins

Oren Froy, Noam Zilberberg, Dalia Gordon, Michael Turkov, Nicolas Gilles, Maria Stankiewicz, Marcel Pelhate, Erwann Loret, Deena A. Oren, Boaz Shaanan, Michael Gurevitz

Research output: Contribution to journalArticlepeer-review

89 Scopus citations

Abstract

Scorpion neurotoxins of the excitatory group show total specificity for insects and serve as invaluable probes for insect sodium channels. However, despite their significance and potential for application in insect-pest control, the structural basis for their bioactivity is still unknown. We isolated, characterized, and expressed an atypically long excitatory toxin, Bj-xtrIT, whose bioactive features resembled those of classical excitatory toxins, despite only 49% sequence identity. With the objective of clarifying the toxic site of this unique pharmacological group, Bj-xtrIT was employed in a genetic approach using point mutagenesis and biological and structural assays of the mutant products. A primary target for modification was the structurally unique C-terminal region. Sequential deletions of C-terminal residues suggested an inevitable significance of Ile73 and Ile74 for toxicity. Based on the bioactive role of the C-terminal region and a comparison of Bj-xtrIT with a Bj-xtrIT-based model of a classical excitatory toxin, AaHIT, a conserved surface comprising the C terminus is suggested to form the site of recognition with the sodium channel receptor.

Original languageEnglish
Pages (from-to)5769-5776
Number of pages8
JournalJournal of Biological Chemistry
Volume274
Issue number9
DOIs
StatePublished - 26 Feb 1999
Externally publishedYes

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