气候变化领域集成服务门户(CCPortal): Structure and selectivity engineering of the M1 muscarinic receptor toxin complex

CCPortal

DOI	10.1126/science.aax2517
	Structure and selectivity engineering of the M1 muscarinic receptor toxin complex
	Maeda S.; Xu J.; N Kadji F.M.; Clark M.J.; Zhao J.; Tsutsumi N.; Aoki J.; Sunahara R.K.; Inoue A.; Garcia K.C.; Kobilka B.K.
发表日期	2020
ISSN	10959203
起始页码	161
结束页码	167
卷号	369 期号:6500
英文摘要	Muscarinic toxins (MTs) are natural toxins produced by mamba snakes that primarily bind to muscarinic acetylcholine receptors (MAChRs) and modulate their function. Despite their similar primary and tertiary structures, MTs show distinct binding selectivity toward different MAChRs. The molecular details of how MTs distinguish MAChRs are not well understood. Here, we present the crystal structure of M1AChR in complex with MT7, a subtype-selective anti-M1AChR snake venom toxin. The structure reveals the molecular basis of the extreme subtype specificity of MT7 for M1AChR and the mechanism by which it regulates receptor function. Through in vitro engineering of MT7 finger regions that was guided by the structure, we have converted the selectivity from M1AChR toward M2AChR, suggesting that the three-finger fold is a promising scaffold for developing G protein-coupled receptor modulators. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
关键词	atropine m1-toxin muscarinic M1 receptor muscarinic receptor blocking agent snake venom animal chemistry genetic engineering genetics protein conformation Sf9 cell line X ray crystallography Animals Atropine Crystallography, X-Ray Elapid Venoms Genetic Engineering Muscarinic Antagonists Protein Conformation Receptor, Muscarinic M1 Sf9 Cells
语种	英语
来源机构	Science (New York, N.Y.)
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/133364
推荐引用方式 GB/T 7714	Maeda S.,Xu J.,N Kadji F.M.,et al. Structure and selectivity engineering of the M1 muscarinic receptor toxin complex[J]. Science (New York, N.Y.),2020,369(6500).
APA	Maeda S..,Xu J..,N Kadji F.M..,Clark M.J..,Zhao J..,...&Kobilka B.K..(2020).Structure and selectivity engineering of the M1 muscarinic receptor toxin complex.,369(6500).
MLA	Maeda S.,et al."Structure and selectivity engineering of the M1 muscarinic receptor toxin complex".369.6500(2020).