Functional Anatomy of Scorpion Toxins Affecting Sodium Channels

Abstract

Long chain scorpion toxins (made of 60 to 70 amino acids) acting on voltage-gated sodium channels in excitable cells are responsible for human envenomation, and comprise a-toxins that inhibit sodium current inactivation and p-toxins, that modify the activation process. These toxins may be further divided according to their pharmacological activities. Thus, a-toxins highly active on mammals or insects, as well as α like toxins may be distinguished within the α-toxin class. The β-toxin class includes toxins active on mammals and, as a separate group, the excitatory and depressant toxins active exclusively on insects. All these toxins possess 4 disulfide bridges and share 15 similar non cystine residues. Accordingly, their 3D structure is highly conserved, comprising an α-helix and a triple stranded β-sheet. The most solvent exposed turns of this structure are prone to insertions or deletions, and accordingly correspond to the most structurally variable regions of the toxins. They have been tested by chemical modification (on several toxins) and site-directed mutagenesis analysis (of LqhαIT) for their possible involvement in the interactions with sodium channels.