Three-finger alpha-neurotoxins and the nicotinic acetylcholine receptor, forty years on.

The discovery, about forty years ago, of alpha-bungarotoxin, a three-finger alpha-neurotoxin from Bungarus multicinctus venom, enabled the isolation of the nicotinic acetylcholine receptor (nAChR), making it one of the most thoroughly characterized receptors today. Since then, the sites of interaction between alpha-neurotoxins and nAChRs have largely been delineated, revealing the remarkable plasticity of the three-finger toxin fold that has optimally evolved to utilize different combinations of functional groups to generate a panoply of target specificities to discern subtle differences between nAChR subtypes. New facets in toxinology have now broadened the scope for the use of alpha-neurotoxins in scientific discovery.