G蛋白偶联受体
联轴节(管道)
计算生物学
化学
选择性
生物信息学
生物
受体
生物化学
工程类
催化作用
机械工程
作者
Ikuo Masuho,Ryoji Kise,Pablo Gaínza,Ee Von Moo,Xiaona Li,Ryosuke Tany,Hideko Wakasugi-Masuho,Bruno E. Correia,Kirill A. Martemyanov
出处
期刊:Cell Reports
[Elsevier]
日期:2023-09-23
卷期号:42 (10): 113173-113173
被引量:59
标识
DOI:10.1016/j.celrep.2023.113173
摘要
G protein-coupled receptors (GPCRs) convert extracellular stimuli into intracellular signaling by coupling to heterotrimeric G proteins of four classes: Gi/o, Gq, Gs, and G12/13. However, our understanding of the G protein selectivity of GPCRs is incomplete. Here, we quantitatively measure the enzymatic activity of GPCRs in living cells and reveal the G protein selectivity of 124 GPCRs with the exact rank order of their G protein preference. Using this information, we establish a classification of GPCRs by functional selectivity, discover the existence of a G12/13-coupled receptor, G15-coupled receptors, and a variety of subclasses for Gi/o-, Gq-, and Gs-coupled receptors, culminating in development of the predictive algorithm of G protein selectivity. We further identify the structural determinants of G protein selectivity, allowing us to synthesize non-existent GPCRs with de novo G protein selectivity and efficiently identify putative pathogenic variants.
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