G-protein activation by a metabotropic glutamate receptor.

ABSTRACT: Family C G-protein-coupled receptors (GPCRs) operate as obligate dimers with extracellular domains that recognize small ligands, leading to G-protein activation on the transmembrane (TM) domains of these receptors by an unknown mechanism¹. Here we show structures of homodimers of the family C metabotropic glutamate receptor 2 (mGlu2) in distinct functional states and in complex with heterotrimeric G_i. Upon activation of the extracellular domain, the two transmembrane domains undergo extensive rearrangement in relative orientation to establish an asymmetric TM6-TM6 interface that promotes conformational changes in the cytoplasmic domain of one protomer. Nucleotide-bound G_i can be observed pre-coupled to inactive mGlu2, but its transition to the nucleotide-fr

SUBMITTER: Seven AB 

PROVIDER: S-EPMC8822903 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature