1seg

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Crystal structure of a toxin chimera between Lqh-alpha-IT from the scorpion Leiurus quinquestriatus hebraeus and AAH2 from Androctonus australis hector

Overview

Scorpion alpha-toxins are similar in their mode of action and, three-dimensional structure but differ considerably in affinity for, various voltage-gated sodium channels (NaChs). To clarify the molecular, basis of the high potency of the alpha-toxin LqhalphaIT (from Leiurus, quinquestriatus hebraeus) for insect NaChs, we identified by mutagenesis, the key residues important for activity. We have found that the functional, surface is composed of two distinct domains: a conserved "Core-domain", formed by residues of the loops connecting the secondary structure, elements of the molecule core and a variable "NC-domain" formed by a, five-residue turn (residues 8-12) and a C-terminal segment (residues, 56-64). We further analyzed the role of these domains in toxin activity on, insects by their stepwise construction onto the scaffold of the, anti-mammalian alpha-toxin, Aah2 (from Androctonus australis hector). The, chimera harboring both domains, Aah2(LqhalphaIT(face)), was as active to, insects as LqhalphaIT. Structure determination of Aah2(LqhalphaIT(face)), by x-ray crystallography revealed that the NC-domain deviates from that of, Aah2 and forms an extended protrusion off the molecule core as appears in, LqhalphaIT. Notably, such a protrusion is observed in all alpha-toxins, active on insects. Altogether, the division of the functional surface into, two domains and the unique configuration of the NC-domain illuminate the, molecular basis of alpha-toxin specificity for insects and suggest a, putative binding mechanism to insect NaChs.

About this Structure

1SEG is a Single protein structure of sequence from Androctonus australis hector with SO4, NO3 and PPI as ligands. Full crystallographic information is available from OCA.

Reference

Molecular basis of the high insecticidal potency of scorpion alpha-toxins., Karbat I, Frolow F, Froy O, Gilles N, Cohen L, Turkov M, Gordon D, Gurevitz M, J Biol Chem. 2004 Jul 23;279(30):31679-86. Epub 2004 May 8. PMID:15133045

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