Structural mechanism underlying G protein family-specific regulation of G protein-gated inwardly rectifying potassium channel.

ABSTRACT: G protein-gated inwardly rectifying potassium channel (GIRK) plays a key role in regulating neurotransmission. GIRK is opened by the direct binding of the G protein ?? subunit (G??), which is released from the heterotrimeric G protein (G???) upon the activation of G protein-coupled receptors (GPCRs). GIRK contributes to precise cellular responses by specifically and efficiently responding to the Gi/o-coupled GPCRs. However, the detailed mechanisms underlying this family-specific and efficient activation are largely unknown. Here, we investigate the structural mechanism underlying the Gi/o family-specific activation of GIRK, by combining cell-based BRET experiments and NMR analyses in a reconstituted membrane environment. We show that the interaction formed by the ?A helix of G?i/o mediates the formation of the G?i/o??-GIRK complex, which is responsible for the family-specific activation of GIRK. We also present a model structure of the G?i/o??-GIRK complex, which provides the molecular basis underlying the specific and efficient regulation of GIRK.

SUBMITTER: Kano H 

PROVIDER: S-EPMC6494913 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature