Key result
Charge reversal substitutions at the VSM of domain III increased the activity of scorpion alpha- and beta-toxins, suggesting allosteric interactions among voltage-sensor modules during channel gating.
Demonstrates allosteric interactions between voltage-sensing modules of sodium channels during gating using scorpion toxins.
Gating of voltage-dependent sodium channels involves coordinated movements of the voltage sensors in the voltage-sensing modules (VSMs) of the four domains (DI-DIV) in response to membrane depolarization. Zhu et al. have recently examined the effects of charge reversal substitutions at the VSM of domain III on the action of scorpion alpha- and beta-toxins that intercept the voltage sensors in domains IV and II, respectively. The increased activity of both toxin types on the mutant channels has suggested that the VSM module at domain III interacts allosterically with the VSM modules in domains IV and II during channel gating thus affecting indirectly the action of both scorpion toxin classes.
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Gurevitz et al. (2022) studied this question. Charge reversal substitutions at the VSM of domain III was evaluated on Toxin activity and allosteric interactions among voltage-sensor modules. Charge reversal substitutions at the VSM of domain III increased the activity of scorpion alpha- and beta-toxins, suggesting allosteric interactions among voltage-sensor modules during channel gating.
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