Global S&T Development Trend Analysis Platform of Resources and Environment
DOI | 10.1126/science.aax2517 |
Structure and selectivity engineering of the M1 muscarinic receptor toxin complex | |
Shoji Maeda; Jun Xu; Francois Marie N. Kadji; Mary J. Clark; Jiawei Zhao; Naotaka Tsutsumi; Junken Aoki; Roger K. Sunahara; Asuka Inoue; K. Christopher Garcia; Brian K. Kobilka | |
2020-07-10 | |
发表期刊 | Science
![]() |
出版年 | 2020 |
英文摘要 | Developing drugs that target a specific subtype in a G protein–coupled receptor (GPCR) family is a major challenge. Maeda et al. examined the basis of specificity of a snake venom toxin binding to muscarinic acetylcholine receptors (MAChRs), which mediate many functions of the central and parasympathetic nervous systems. They determined a structure that shows why the mamba venom toxin MT7 is specific for one receptor, M1AChR, and also explains how it inhibits downstream signaling. Based on this structure, they engineered MT7 to be selective for another receptor, M2AChR, instead of M1ChR. The toxin may present a promising scaffold for developing specific GPCR modulators. Science , this issue p. [161][1] 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. [1]: /lookup/doi/10.1126/science.aax2517 |
领域 | 气候变化 ; 资源环境 |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/283396 |
专题 | 气候变化 资源环境科学 |
推荐引用方式 GB/T 7714 | Shoji Maeda,Jun Xu,Francois Marie N. Kadji,et al. Structure and selectivity engineering of the M1 muscarinic receptor toxin complex[J]. Science,2020. |
APA | Shoji Maeda.,Jun Xu.,Francois Marie N. Kadji.,Mary J. Clark.,Jiawei Zhao.,...&Brian K. Kobilka.(2020).Structure and selectivity engineering of the M1 muscarinic receptor toxin complex.Science. |
MLA | Shoji Maeda,et al."Structure and selectivity engineering of the M1 muscarinic receptor toxin complex".Science (2020). |
条目包含的文件 | 条目无相关文件。 |
除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。
修改评论