Molecular mechanism of GIRK2 channel gating modulated by cholesteryl hemisuccinate.

ABSTRACT: Cholesterol, an essential lipid of cell membranes, regulates G protein-gated inwardly rectifying potassium (GIRK) channel activity. Previous studies have shown that cholesterol activates GIRK2 homotetrameric channels, which are expressed in dopaminergic neurons of the brain. Deletion of GIRK2 channels affects both GIRK2 homo- and heterotetrames and can lead to abnormal neuronal excitability, including conditions such as epilepsy and addiction. A 3.5 Å cryo-EM structure of GIRK2 in complex with CHS (cholesteryl hemisuccinate) and PIP₂ (phosphatidylinositol 4,5-bisphosphate) has been solved. This structure provides the opportunity to study GIRK2 channel gating dynamics regulated by cholesterol using gating molecular dynamics (GMD) simulations. In the present study, we conducted mi

SUBMITTER: Cui M 

PROVIDER: S-EPMC11527606 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature