Cryo-EM analysis of PIP₂ regulation in mammalian GIRK channels.

ABSTRACT: G-protein-gated inward rectifier potassium (GIRK) channels are regulated by G proteins and PIP₂. Here, using cryo-EM single particle analysis we describe the equilibrium ensemble of structures of neuronal GIRK2 as a function of the C8-PIP₂ concentration. We find that PIP₂ shifts the equilibrium between two distinguishable structures of neuronal GIRK (GIRK2), extended and docked, towards the docked form. In the docked form the cytoplasmic domain, to which G_βγ binds, becomes accessible to the cytoplasmic membrane surface where G_βγ resides. Furthermore, PIP₂ binding reshapes the G_βγ binding surface on the cytoplasmic domain, preparing it to receive G_βγ. We find that cardiac GIRK (GIRK1/4) can also exist in

SUBMITTER: Niu Y 

PROVIDER: S-EPMC7556866 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature