期刊
NATURE CHEMICAL BIOLOGY
卷 11, 期 2, 页码 134-U76出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/NCHEMBIO.1711
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资金
- National Natural Science Foundation of China [31130028, 31225011]
- Ministry of Science and Technology [2012CB518000]
- Program for Introducing Talents of Discipline to the Universities of the Ministry of Education [B08029]
- Merieux Research Grants Program of the Institut Merieux
- Centre National de la Recherche Scientifique
- Institut National de la Sante et de la Recherche Medicale
- Agence Nationale de la Recherche [ANR-09-PIRI-0011]
- Fondation pour la Recherche Medicale (Equipe FRM) [DEQ20130326522]
- Fondation Bettencourt Schueller
- French Embassy in China
- FEBS long-term fellowship
- Agencia de Gestio d'Ajuts Universitaris i de Recerca (AGAUR) BP post-doctoral fellowship
- Agence Nationale de la Recherche (ANR) [ANR-09-PIRI-0011] Funding Source: Agence Nationale de la Recherche (ANR)
G protein-coupled receptors (GPCRs) are major players in cell communication. Although they form functional monomers, increasing evidence indicates that GPCR dimerization has a critical role in cooperative phenomena that are important for cell signal integration. However, the structural bases of these phenomena remain elusive. Here, using well-characterized receptor dimers, the metabotropic glutamate receptors (mGluRs), we show that structural changes at the dimer interface are linked to receptor activation. We demonstrate that the main dimer interface is formed by transmembrane a helix 4 (TM4) and TM5 in the inactive state and by TM6 in the active state. This major change in the dimer interface is required for receptor activity because locking the TM4-TM5 interface prevents activation by agonist, whereas locking the TM6 interface leads to a constitutively active receptor. These data provide important information on the activation mechanism of mGluRs and improve our understanding of the structural basis of the negative cooperativity observed in these GPCR dimers.
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