Structure of an open K_ATP channel reveals tandem PIP₂ binding sites mediating the Kir6.2 and SUR1 regulatory interface.

ABSTRACT: ATP-sensitive potassium (K_ATP) channels, composed of four pore-lining Kir6.2 subunits and four regulatory sulfonylurea receptor 1 (SUR1) subunits, control insulin secretion in pancreatic β-cells. K_ATP channel opening is stimulated by PIP₂ and inhibited by ATP. Mutations that increase channel opening by PIP₂ reduce ATP inhibition and cause neonatal diabetes. Although considerable evidence has implicated a role for PIP₂ in K_ATP channel function, previously solved open-channel structures have lacked bound PIP₂, and mechanisms by which PIP₂ regulates K_ATP channels remain unresolved. Here, we report the cryoEM structure of a K_ATP channel harboring the neonatal diabetes mutation Kir6.2-Q

SUBMITTER: Driggers CM 

PROVIDER: S-EPMC10954709 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature