Molecular characterization of the specificity of interactions of various neurotoxins on two distinct nicotinic acetylcholine receptors

Snake curaremimetic toxins are currently classified as short-chain and long -chain toxins according to their size and their number of disulfide bonds. All these toxins bind with high affinity to muscular-type nicotinic acetylc holine receptor, whereas only long toxins recognize the alpha 7 receptor wi th high affinity. On the basis of binding experiments with Torpedo or neuro nal alpha 7 receptors using wild-type and mutated neurotoxins, we character ized the molecular determinants involved in these different recognition pro cesses. The functional sites by which long and short toxins interact with t he muscular-type receptor include a common core of highly conserved residue s and residues that are specific to each of toxin families. Furthermore, th e functional sites through which alpha-cobratoxin, a long-chain toxin, inte racts with muscular and alpha 7 receptors share similarities but also marke d differences. Our results reveal that the three-finger fold toxins have ev olved toward various specificities by displaying distinct functional sites. (C) 2000 Elsevier Science B.V. All rights reserved.