Molecular characterization of the specificity of interactions of various neurotoxins on two distinct nicotinic acetylcholine receptors
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- 作者：Servent ; Denis ; Antil-Delbeke ; Sté ; phanie ; Gaillard ; Carole ; Corringer ; Pierre-Jean ; et. al.
- 关键词：Nicotinic acetylcholine receptor ; Neurotoxin ; α ; -Cobratoxin
- 刊名：European Journal of Pharmacology
- 出版年：2000
- 出版时间：March 30, 2000
- 年：2000
- 卷：393
- 期：1-3
- 页码：197-204
- 全文大小：1.01 M
文摘
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 acetylcholine receptor, whereas only long toxins recognize the α7 receptor with high affinity. On the basis of binding experiments with Torpedo or neuronal α7 receptors using wild-type and mutated neurotoxins, we characterized the molecular determinants involved in these different recognition processes. The functional sites by which long and short toxins interact with the muscular-type receptor include a common core of highly conserved residues and residues that are specific to each of toxin families. Furthermore, the functional sites through which α-cobratoxin, a long-chain toxin, interacts with muscular and α7 receptors share similarities but also marked differences. Our results reveal that the three-finger fold toxins have evolved toward various specificities by displaying distinct functional sites.