Allosteric control of an asymmetric transduction in a G protein-coupled receptor heterodimer

被引：47

作者：

Liu, Junke ^{[1
,2
]}

Zhang, Zongyong ^{[1
,2
]}

Moreno-Delgado, David ^{[3
]}

Dalton, James A. R. ^{[4
,5
,6
]}

Rovira, Xavier ^{[3
]}

Trapero, Ana ^{[7
]}

Goudet, Cyril ^{[3
]}

Llebaria, Amadeu ^{[7
]}

Giraldo, Jesus ^{[4
,5
,6
]}

Yuan, Qilin ^{[1
,2
]}

Rondard, Philippe ^{[3
]}

Huang, Siluo ^{[1
,2
]}

Liu, Jianfeng ^{[1
,2
]}

Pin, Jean-Philippe ^{[3
]}

机构：

[1] Huazhong Univ Sci & Technol, Coll Life Sci & Technol, Collaborat Innovat Ctr Genet & Dev, Minist Educ, Wuhan, Hubei, Peoples R China

[2] Huazhong Univ Sci & Technol, Minist Educ, Key Lab Mol Biophys, Wuhan, Hubei, Peoples R China

[3] Univ Montpellier, CNRS, INSERM, Inst Genom Fonct, Montpellier, France

[4] Univ Autonoma Barcelona, Inst Neurociencies, Baracaldo, Spain

[5] Univ Autonoma Barcelona, Unitat Bioestadist, Baracaldo, Spain

[6] Network Biomed Res Ctr Mental Hlth, Barcelona, Spain

[7] IQAC CSIC, Inst Adv Chem Catalonia, Lab Med Chem & Synth, MCS, Barcelona, Spain

来源：

ELIFE | 2017年 / 6卷

基金：

中国国家自然科学基金;

关键词：

METABOTROPIC GLUTAMATE RECEPTORS; TIME-RESOLVED FRET; A GPCR DIMERS; CONFORMATIONAL DYNAMICS; HEPTAHELICAL DOMAIN; UNIFYING MECHANISM; CRYSTAL-STRUCTURE; CNS DISORDERS; ACTIVATION; MODULATORS;

D O I：

10.7554/eLife.26985

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

GPCRs play critical roles in cell communication. Although GPCRs can form heteromers, their role in signaling remains elusive. Here we used rat metabotropic glutamate (mGlu) receptors as prototypical dimers to study the functional interaction between each subunit. mGluRs can form both constitutive homo- and heterodimers. Whereas both mGlu2 and mGlu4 couple to G proteins, G protein activation is mediated by mGlu4 heptahelical domain (HD) exclusively in mGlu2-4 heterodimers. Such asymmetric transduction results from the action of both the dimeric extracellular domain, and an allosteric activation by the partially-activated non-functional mGlu2 HD. G proteins activation by mGlu2 HD occurs if either the mGlu2 HD is occupied by a positive allosteric modulator or if mGlu4 HD is inhibited by a negative modulator. These data revealed an oriented asymmetry in mGlu heterodimers that can be controlled with allosteric modulators. They provide new insight on the allosteric interaction between subunits in a GPCR dimer.

引用

页数：19

共 66 条

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