期刊
EMBO JOURNAL
卷 29, 期 21, 页码 3646-3659出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/emboj.2010.236
关键词
G protein; G-protein-coupled receptor; heterodimerization; molecular organization; RGS
资金
- SERVIER
- Fondation Recherche Medicale ('Equipe FRM')
- Fondation pour la Recherche sur le Cerveau (FRC) Neurodon
- Institut National de la Sante et de la Recherche Medicale (INSERM)
- Centre National de la Recherche Scientifique (CNRS)
- Wellcome Trust
- GACR [309/06/1304]
- Swiss Science Foundation [3100A0-117816]
- EGID
Functional asymmetry of G-protein-coupled receptor (GPCR) dimers has been reported for an increasing number of cases, but the molecular architecture of signalling units associated to these dimers remains unclear. Here, we characterized the molecular complex of the melatonin MT1 receptor, which directly and constitutively couples to G(i) proteins and the regulator of G-protein signalling (RGS) 20. The molecular organization of the ternary MT1/G(i)/RGS20 complex was monitored in its basal and activated state by bioluminescence resonance energy transfer between probes inserted at multiple sites of the complex. On the basis of the reported crystal structures of G(i) and the RGS domain, we propose a model wherein one G(i) and one RGS20 protein bind to separate protomers of MT1 dimers in a pre-associated complex that rearranges upon agonist activation. This model was further validated with MT1/MT2 heterodimers. Collectively, our data extend the concept of asymmetry within GPCR dimers, reinforce the notion of receptor specificity for RGS proteins and highlight the advantage of GPCRs organized as dimers in which each protomer fulfils its specific task by binding to different GPCR-interacting proteins. The EMBO Journal (2010) 29, 3646-3659. doi:10.1038/emboj.2010.236; Published online 21 September 2010
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据