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Diversification of neurotoxins by C-tail ‘wiggling’: a scorpion recipe for survival

Departments of Plant Sciences and
^* Biochemistry, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Ramat-Aviv 69978, Tel-Aviv, Israel

¹Correspondence: Department of Plant Sciences at the Faculty of Life Sciences, Tel-Aviv University, Britania Bldg., Rm. 506, Ramat-Aviv 69978, Tel-Aviv, Israel. E-mail: mamgur{at}post.tau.ac.il

ABSTRACT

The structure of bioactive surfaces of proteins is a subject of intensive research, yet the mechanisms by which such surfaces have evolved are largely unknown. Polypeptide toxins produced by venomous animals such as sea anemones, cone snails, scorpions, and snakes show multiple routes for active site diversification, each maintaining a typical conserved scaffold. Comparative analysis of an array of genetically related scorpion polypeptide toxins that modulate sodium channels in neuronal membranes suggests a unique route of toxic site diversification. This premise is based on recent identification of bioactive surfaces of toxin representative of three distinct pharmacological groups and a comparison of their 3-dimensional structures. Despite their similar scaffold, the bioactive surfaces of the various toxins vary considerably, but always coincide with the molecular exterior onto which the C-tail is anchored. Superposition of the toxin structures indicates that the C-tails diverge from a common structural start point, which suggests that the pharmacological versatility displayed by these toxins might have been achieved along evolution via structural reconfiguration of the C-tail, leading to reshaping of new bioactive surfaces.—Gurevitz, M., Gordon, D., Ben-Natan, S., Turkov, M., Froy, O. Diversification of neurotoxins by C-tail ‘wiggling’: a scorpion recipe for survival.

Key Words: toxic polypeptides • scorpion neurotoxin • bioactive surface

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