Rearrangement of the transmembrane domain interfaces associated with the activation of a GPCR hetero-oligomer.

ABSTRACT: 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_B1 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 interfa

SUBMITTER: Xue L 

PROVIDER: S-EPMC6591306 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature