Structural Insights into the Process of GPCR-G Protein Complex Formation

被引：119

作者：

Liu, Xiangyu ^{[1
]}

Xu, Xinyu ^{[1
]}

Hilger, Daniel ^{[2
]}

Aschauer, Philipp ^{[3
]}

Tiemann, Johanna K. S. ^{[4
,5
]}

Du, Yang ^{[2
]}

Liu, Hongtao ^{[1
]}

Hirata, Kunio ^{[6
,7
]}

Sun, Xiaoou ^{[1
]}

Guixa-Gonzalez, Ramon ^{[4
,9
]}

Mathiesen, Jesper M. ^{[8
]}

Hildebrand, Peter W. ^{[4
,5
]}

Kobilka, Brian K. ^{[1
,2
]}

机构：

[1] Tsinghua Univ, Tsinghua Peking Joint Ctr Life Sci, Beijing Adv Innovat Ctr Struct Biol, Sch Med, Beijing 100084, Peoples R China

[2] Stanford Univ, Dept Mol & Cellular Physiol, Sch Med, Stanford, CA 94305 USA

[3] Karl Franzens Univ Graz, Inst Mol Biosci, Humboldtstr 50-3, A-8010 Graz, Austria

[4] Charite Med Univ Berlin, Inst Med Phys & Biophys, D-10117 Berlin, Germany

[5] Univ Leipzig, Fac Med, Inst Med Phys & Biophys, D-04107 Leipzig, Germany

[6] RIKEN, SR Life Sci Instrumentat Unit, Adv Photon Technol Div, Res Infrastruct Grp,SPring 8 Ctr, 1-1-1 Kouto, Sayo, Hyogo 6795148, Japan

[7] Japan Sci & Technol Agcy, Precursory Res Embryon Sci & Technol PRESTO, 4-1-8 Honcho, Kawaguchi, Saitama 3320012, Japan

[8] Univ Copenhagen, Fac Med & Hlth Sci, Dept Drug Design & Pharmacol, DK-2100 Copenhagen, Denmark

[9] Autonomous Univ Barcelona, Fac Med, Biostat Unit, Lab Computat Med, Bellaterra 08193, Spain

来源：

CELL | 2019年 / 177卷 / 05期

关键词：

CRYO-EM STRUCTURE; FORCE-FIELD; ADRENERGIC-RECEPTOR; CRYSTAL-STRUCTURE; LIGAND EFFICACY; VALIDATION; BILAYER;

D O I：

10.1016/j.cell.2019.04.021

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The crystal structure of the beta 2-adrenergic receptor (beta 2AR) bound to the G protein adenylyl cyclase stimulatory G protein (Gs) captured the complex in a nucleotide-free state (beta 2AR-Gs(empty)). Unfortunately, the beta 2AR-Gs(empty) complex does not provide a clear explanation for G protein coupling specificity. Evidence from several sources suggests the existence of a transient complex between the beta 2AR and GDP-bound Gs protein (beta 2AR-Gs(GDP) ) that may represent an intermediate on the way to the formation of beta 2AR-Gs(empty) and may contribute to coupling specificity. Here we present a structure of the beta 2AR in complex with the carboxyl terminal 14 amino acids from G alpha s along with the structure of the GDP-bound Gs heterotrimer. These structures provide evidence for an alternate interaction between the beta 2AR and Gs that may represent an intermediate that contrib- utes to Gs coupling specificity.

引用

页码：1243 / +

页数：21

共 49 条

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