Journal
NATURE COMMUNICATIONS
Volume 10, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-019-10834-5
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Funding
- Ministry of Science and Technology [2018YFA0507003]
- National Natural Science Foundation of China (NSFC) [81720108031, 81872945, 31721002, 31420103909]
- 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 (CNRS)
- Institut National de la Sante et de la Recherche Medicale (INSERM)
- Agence Nationale de la Recherche [ANR-09-PIRI-0011]
- FRM [Equipe FRM DEQ20130326522, DEQ20170336747]
- French Embassy in China
- Agencia de Gestio d'Ajuts Universitaris i de Recerca (AGAUR)
- Spanish Ministry of Economy, Industry and Competitiveness [SAF2015-74132-JIN]
- PO FEDER of Catalonia 2014-2020 [001-P-000382]
- Agence Nationale de la Recherche (ANR) [ANR-09-PIRI-0011] Funding Source: Agence Nationale de la Recherche (ANR)
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G protein-coupled receptors (GPCRs) can integrate extracellular signals via allosteric interactions within dimers and higher-order oligomers. However, the structural bases of these interactions remain unclear. Here, we use the GABA(B) receptor heterodimer as a model as it forms large complexes in the brain. It is subjected to genetic mutations mainly affecting transmembrane 6 (TM6) and involved in human diseases. By cross-linking, we identify the transmembrane interfaces involved in GABA(B1)-GABA(B2), as well as GABA(B1)-GABA(B2) interactions. Our data are consistent with an oligomer made of a row of GABA(B1). We bring evidence that agonist activation induces a concerted rearrangement of the various interfaces. While the GB1-GB2 interface is proposed to involve TM5 in the inactive state, cross-linking of TM6s lead to constitutive activity. These data bring insight for our understanding of the allosteric interaction between GPCRs within oligomers.
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