自然杂志 >

2021 , Vol. 43 >Issue 1: 45 - 52

DOI: https://doi.org/10.3969/j.issn.0253-9608.2021.01.007

专题综述

G蛋白偶联受体的共同激活机制

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  • ①复旦大学 基础医学院，上海 200032；②上海科技大学 iHuman研究所，上海 201210；③上海科技大学 生命科 学与技术学院，上海 201210 

收稿日期: 2020-10-01

  网络出版日期: 2021-02-25

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Common activation mechanism of GPCR

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  • ①School of Basic Medical Sciences, Fudan University, Shanghai 200032, China; ②iHuman Institute, ShanghaiTech University, Shanghai 201210, China; ③School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China

Received date: 2020-10-01

  Online published: 2021-02-25

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摘要

G蛋白偶联受体(G protein-coupled receptor, GPCR)构成人体中最庞大的膜蛋白家族，也是最重要的一类药物靶 标。随着GPCR结构解析技术的突破，目前已破解八十余个受体的400多个结构，揭示出GPCR复杂多样的配体结合模式和 跨膜信号转导机制。近年来，残基相互作用计算已实现对GPCR构象变化的精细描述，揭示出A家族GPCR存在共同的激活 机制。文章简要回顾GPCR激活机制研究的方法和创新点，并对A家族GPCR共同激活机制如何推动功能研究和药物研发进行展望。

关键词：  ; G蛋白偶联受体; 激活机制; 别构调控; 药物开发

本文引用格式

周庆同, 戴之卓, 赵素文 . G蛋白偶联受体的共同激活机制[J]. 自然杂志, 2021 , 43(1) : 45 -52 . DOI: 10.3969/j.issn.0253-9608.2021.01.007

Abstract

G protein-coupled receptor (GPCR) family is the largest and most diverse group of membrane receptors in eukaryotes. By mediating a wide variety of physiological functions, GPCRs are important drug targets with around 500 marketed drugs. The breakthrough of GPCR structural studies leads to the determinations of over 400 structures, which highlights the diversified ligandbinding modes and signal transduction mechanisms across GPCRs. In recent years, a common activation mechanism of class A GPCRs has been discovered, by using residue-residue contact score (RRCS) that can quantitatively describes the rearrangements of residue contacts upon receptor activation. Here, we briefly summarize the approaches utilized in GPCR activation mechanism, and also discuss the significance of understanding GPCR activation mechanism on functional studies and drug discovery. 

Key words： G protein-coupled receptor, activation mechanism, allostery, drug discovery

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