Structural mechanism of G protein activation by G protein-coupled receptor

被引:63
作者
Nguyen Minh Duc [1 ]
Kim, Hee Ryung [1 ]
Chung, Ka Young [1 ]
机构
[1] Sungkyunkwan Univ, Sch Pharm, 2066 Seobu Ro, Suwon 440746, South Korea
基金
新加坡国家研究基金会;
关键词
GPCR; G protein; Structure; HETEROTRIMERIC G-PROTEIN; RHODOPSIN-TRANSDUCIN INTERACTIONS; CATALYZED NUCLEOTIDE EXCHANGE; MYRISTOYLATED AMINO-TERMINUS; BETA(2) ADRENERGIC-RECEPTOR; COVALENT CROSS-LINKING; GTP-GAMMA-S; ALPHA-SUBUNIT; CRYSTAL-STRUCTURE; PHOTOACTIVATED RHODOPSIN;
D O I
10.1016/j.ejphar.2015.05.016
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
G protein-coupled receptors (GPCRs) are a family of membrane receptors that regulate physiology and pathology of various organs. Consequently, about 40% of drugs in the market targets GPCRs. Heterotrimeric G proteins are composed of alpha, beta, and gamma subunits, and act as the key downstream signaling molecules of GPCRs. The structural mechanism of G protein activation by GPCRs has been of a great interest, and a number of biochemical and biophysical studies have been performed since the late 80's. These studies investigated the interface between GPCR and G proteins and the structural mechanism of GPCR-induced G protein activation. Recently, arrestins are also reported to be important molecular switches in GPCR-mediated signal transduction, and the physiological output of arrestin-mediated signal transduction is different from that of G protein-mediated signal transduction. Understanding the structural mechanism of the activation of G proteins and arrestins would provide fundamental information for the downstream signaling-selective GPCR-targeting drug development. This review will discuss the structural mechanism of GPCR-incluced G protein activation by comparing previous biochemical and biophysical studies. (C) 2015 Elsevier B.V. All rights reserved.
引用
收藏
页码:214 / 222
页数:9
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