Structural insights into GIRK2 channel modulation by cholesterol and PIP₂.

ABSTRACT: G-protein-gated inwardly rectifying potassium (GIRK) channels are important for determining neuronal excitability. In addition to G proteins, GIRK channels are potentiated by membrane cholesterol, which is elevated in the brains of people with neurodegenerative diseases such as Alzheimer's dementia and Parkinson's disease. The structural mechanism of cholesterol modulation of GIRK channels is not well understood. In this study, we present cryo- electron microscopy (cryoEM) structures of GIRK2 in the presence and absence of the cholesterol analog cholesteryl hemisuccinate (CHS) and phosphatidylinositol 4,5-bisphosphate (PIP₂). The structures reveal that CHS binds near PIP₂ in lipid-facing hydrophobic pockets of the transmembrane domain. Our structural analysis suggests

SUBMITTER: Mathiharan YK 

PROVIDER: S-EPMC8436891 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature