Ligand-mediated Structural Dynamics of a Mammalian Pancreatic K_ATP Channel.

ABSTRACT: Regulation of pancreatic K_ATP channels involves orchestrated interactions of their subunits, Kir6.2 and SUR1, and ligands. Previously we reported K_ATP channel cryo-EM structures in the presence and absence of pharmacological inhibitors and ATP, focusing on the mechanisms by which inhibitors act as pharmacological chaperones of K_ATP channels (Martin et al., 2019). Here we analyzed the same cryo-EM datasets with a focus on channel conformational dynamics to elucidate structural correlates pertinent to ligand interactions and channel gating. We found pharmacological inhibitors and ATP enrich a channel conformation in which the Kir6.2 cytoplasmic domain is closely associated with the transmembrane domain, while depleting one where the Kir6.2 cytoplasmic domain

SUBMITTER: Sung MW 

PROVIDER: S-EPMC9618280 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature