Cartier G E, Yoshikami D, Gray W R, Luo S, Olivera B M, McIntosh J M
Department of Biology, University of Utah, Salt Lake City, 84112, USA.
J Biol Chem. 1996 Mar 29;271(13):7522-8. doi: 10.1074/jbc.271.13.7522.
We have isolated a 16-amino acid peptide from the venom of the marine snail Conus magus which potently blocks nicotinic acetylcholine receptors (nAChRs) composed of alpha3beta2 subunits. This peptide, named alpha-conotoxin MII, was identified by electrophysiologically screening venom fractions against cloned nicotinic receptors expressed in Xenopus oocytes. The peptide's structure, which has been confirmed by mass spectrometry and total chemical synthesis, differs significantly from those of all previously isolated alpha-conotoxins. Disulfide bridging, however, is conserved. The toxin blocks the response to acetylcholine in oocytes expressing alpha3beta2 nAChRs with an IC50 of 0.5 nM and is 2-4 orders of magnitude less potent on other nAChR subunit combinations. We have recently reported the isolation and characterization of alpha-conotoxin ImI, which selectively targets homomeric alpha7 neuronal nAChRs. Yet other alpha-conotoxins selectively block the muscle subtype of nAChR. Thus, it is increasingly apparent that alpha-conotoxins represent a significant resource for ligands with which to probe structure-function relationships of various nAChR subtypes.
我们从海蜗牛芋螺的毒液中分离出一种16个氨基酸的肽，它能有效阻断由α3β2亚基组成的烟碱型乙酰胆碱受体（nAChRs）。这种名为α-芋螺毒素MII的肽是通过对非洲爪蟾卵母细胞中表达的克隆烟碱型受体进行电生理筛选毒液组分而鉴定出来的。该肽的结构已通过质谱和全化学合成得到证实，与所有先前分离的α-芋螺毒素有显著差异。然而，二硫键桥是保守的。该毒素在表达α3β2 nAChRs的卵母细胞中阻断对乙酰胆碱的反应，IC50为0.5 nM，对其他nAChR亚基组合的效力低2至4个数量级。我们最近报道了α-芋螺毒素ImI的分离和特性，它选择性地靶向同聚体α7神经元nAChRs。还有其他α-芋螺毒素选择性地阻断nAChR的肌肉亚型。因此，越来越明显的是，α-芋螺毒素是用于探究各种nAChR亚型结构-功能关系的配体的重要来源。
