Energetic analysis of the rhodopsin-G-protein complex links the α5 helix to GDP release

被引：59

作者：

Alexander, Nathan S. ^{[1
]}

Preininger, Anita M. ^{[2
]}

Kaya, Ali I. ^{[2
]}

Stein, Richard A. ^{[3
]}

Hamm, Heidi E. ^{[2
]}

Meiler, Jens ^{[1
,2
]}

机构：

[1] Vanderbilt Univ, Dept Chem, Nashville, TN USA

[2] Vanderbilt Univ, Dept Pharmacol, Nashville, TN 37212 USA

[3] Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA

来源：

NATURE STRUCTURAL & MOLECULAR BIOLOGY | 2014年 / 21卷 / 01期

基金：

美国国家科学基金会; 美国国家卫生研究院;

关键词：

HETEROTRIMERIC G-PROTEINS; BETA(2) ADRENERGIC-RECEPTOR; LIGHT-ACTIVATED RHODOPSIN; GTP-GAMMA-S; CRYSTAL-STRUCTURE; DISTANCE MEASUREMENTS; CONFORMATIONAL-CHANGES; NUCLEOTIDE EXCHANGE; TRANSDUCIN; PREDICTION;

D O I：

10.1038/nsmb.2705

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：

We present a model of interaction of G(i) protein with the activated receptor (R*) rhodopsin, which pinpoints energetic contributions to activation and reconciles the beta(2) adrenergic receptor-G(s) crystal structure with new and previously published experimental data. In silico analysis demonstrated energetic changes when the G alpha C-terminal helix (alpha 5) interacts with the R* cytoplasmic pocket, thus leading to displacement of the helical domain and GDP release. The model features a less dramatic domain opening compared with the crystal structure. The alpha 5 helix undergoes a 63 degrees rotation, accompanied by a 5.7-angstrom translation, that reorganizes interfaces between alpha 5 and alpha 1 helices and between alpha 5 and beta 6-alpha 5. Changes in the beta 6-alpha 5 loop displace alpha G. All of these movements lead to opening of the GDP-binding pocket. The model creates a roadmap for experimental studies of receptor-mediated G-protein activation.

引用

页码：56 / +

页数：10

共 44 条

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