Vascular K_ATP channel structural dynamics reveal regulatory mechanism by Mg-nucleotides.

ABSTRACT: Vascular tone is dependent on smooth muscle K_ATP channels comprising pore-forming Kir6.1 and regulatory SUR2B subunits, in which mutations cause Cantú syndrome. Unique among K_ATP isoforms, they lack spontaneous activity and require Mg-nucleotides for activation. Structural mechanisms underlying these properties are unknown. Here, we determined cryogenic electron microscopy structures of vascular K_ATP channels bound to inhibitory ATP and glibenclamide, which differ informatively from similarly determined pancreatic K_ATP channel isoform (Kir6.2/SUR1). Unlike SUR1, SUR2B subunits adopt distinct rotational "propeller" and "quatrefoil" geometries surrounding their Kir6.1 core. The glutamate/aspartate-rich linker connecting the two halves of the SUR-AB

SUBMITTER: Sung MW 

PROVIDER: S-EPMC8694068 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature