Cryo-EM analysis of PIP<sub>2</sub> regulation in mammalian GIRK channels.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 32844743.
- Also identified by DOI 10.7554/eLife.60552 and PMC identifier 7556866.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
G-protein-gated inward rectifier potassium (GIRK) channels are regulated by G proteins and PIP<sub>2</sub>. Here, using cryo-EM single particle analysis we describe the equilibrium ensemble of structures of neuronal GIRK2 as a function of the C8-PIP<sub>2</sub> concentration. We find that PIP<sub>2</sub> 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<sub>βγ</sub> binds, becomes accessible to the cytoplasmic membrane surface where G<sub>βγ</sub> resides. Furthermore, PIP<sub>2</sub> binding reshapes the G<sub>βγ</sub> binding surface on the cytoplasmic domain, preparing it to receive G<sub>βγ</sub>. We find that cardiac GIRK (GIRK1/4) can also exist in both extended and docked conformations. These findings lead us to conclude that PIP<sub>2</sub> influences GIRK channels in a structurally similar manner to Kir2.2 channels. In Kir2.2 channels, the PIP<sub>2</sub>-induced conformational changes open the pore. In GIRK channels, they prepare the channel for activation by G<sub>βγ</sub>.
Medical subject headings
- G Protein-Coupled Inwardly-Rectifying Potassium Channels
- Phosphatidylinositol 4,5-Diphosphate