Universal allosteric mechanism for Gα activation by GPCRs

被引：283

作者：

Flock, Tilman ^{[1
]}

Ravarani, Charles N. J. ^{[1
]}

Sun, Dawei ^{[2
,3
]}

Venkatakrishnan, A. J. ^{[1
]}

Kayikci, Melis ^{[1
]}

Tate, Christopher G. ^{[1
]}

Veprintsev, Dmitry B. ^{[2
,3
]}

Babu, M. Madan ^{[1
]}

机构：

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

[2] Paul Scherrer Inst, Lab Biomol Res, CH-5232 Villigen, Switzerland

[3] Swiss Fed Inst Technol, Dept Biol, CH-8039 Zurich, Switzerland

来源：

NATURE | 2015年 / 524卷 / 7564期

基金：

英国医学研究理事会; 瑞士国家科学基金会;

关键词：

MULTIPLE SEQUENCE ALIGNMENT; G-PROTEIN ACTIVATION; CRYSTAL-STRUCTURE; STRUCTURAL BASIS; SIGNAL-TRANSDUCTION; BINDING-SITE; WEB SERVER; EVOLUTION; RAS; HELIX;

D O I：

10.1038/nature14663

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 (GPCRs) allosterically activate heterotrimeric G proteins and trigger GDP release. Given that there are similar to 800 human GPCRs and 16 different G alpha genes, this raises the question of whether a universal allosteric mechanism governs G alpha activation. Here we show that different GPCRs interact with and activate G alpha proteins through a highly conserved mechanism. Comparison of G alpha with the small G protein Ras reveals how the evolution of short segments that undergo disorder-to-order transitions can decouple regions important for allosteric activation from receptor binding specificity. This might explain how the GPCR-G alpha system diversified rapidly, while conserving the allosteric activation mechanism.

引用

页码：173 / +

页数：19

共 76 条

[1] Energetic analysis of the rhodopsin-G-protein complex links the α5 helix to GDP release [J].