The putative bioactive surface of insect-selective scorpion excitatory neurotoxins

Scorpion neurotoxins of the excitatory group show total specificity for ins ects and serve as invaluable probes for insect sodium channels. However, de spite their significance and potential for application in insect-pest contr ol, the structural basis for their bioactivity is still unknown. We isolate d, characterized, and expressed an atypically long excitatory toxin, Bj-xtr IT, 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 ass ays of the mutant products. A primary target for modification was the struc turally unique C-terminal region, Sequential deletions of C-terminal residu es suggested an inevitable significance of Ile(73) and Ile(74) 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 si te of recognition with the sodium channel receptor.