Structure of a β1-adrenergic G-protein-coupled receptor

被引：1135

作者：

Warne, Tony ^{[1
]}

Serrano-Vega, Maria J. ^{[1
]}

Baker, Jillian G. ^{[2
]}

Moukhametzianov, Rouslan ^{[1
]}

Edwards, Patricia C. ^{[1
]}

Henderson, Richard ^{[1
]}

Leslie, Andrew G. W. ^{[1
]}

Tate, Christopher G. ^{[1
]}

Schertler, Gebhard F. X. ^{[1
]}

机构：

[1] MRC, Mol Biol Lab, Cambridge CB2 0QH, England

[2] Univ Nottingham, Inst Cell Signalling, Sch Med, Queens Med Ctr, Nottingham NG7 2UH, England

来源：

NATURE | 2008年 / 454卷 / 7203期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

D O I：

10.1038/nature07101

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

G-protein-coupled receptors have a major role in transmembrane signalling in most eukaryotes and many are important drug targets. Here we report the 2.7 angstrom resolution crystal structure of a beta(1)-adrenergic receptor in complex with the high-affinity antagonist cyanopindolol. The modified turkey (Meleagris gallopavo) receptor was selected to be in its antagonist conformation and its thermostability improved by earlier limited mutagenesis. The ligand-binding pocket comprises 15 side chains from amino acid residues in 4 transmembrane alpha-helices and extracellular loop 2. This loop defines the entrance of the ligand-binding pocket and is stabilized by two disulphide bonds and a sodium ion. Binding of cyanopindolol to the beta(1)-adrenergic receptor and binding of carazolol to the beta(2)-adrenergic receptor involve similar interactions. A short well-defined helix in cytoplasmic loop 2, not observed in either rhodopsin or the beta(2)-adrenergic receptor, directly interacts by means of a tyrosine with the highly conserved DRY motif at the end of helix 3 that is essential for receptor activation.

引用

页码：486 / 491

页数：6

共 52 条

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