ATP-sensitive potassium channels: novel potential roles in Parkinson's disease.
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ABSTRACT:
SUBMITTER: Zeng J
PROVIDER: S-EPMC5550652 | biostudies-other | 2007 Nov
REPOSITORIES: biostudies-other
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Project description:ATP-sensitive potassium (K-ATP) channels composed of a pore-forming Kir6.2 potassium channel and a regulatory ABC transporter sulfonylurea receptor 1 (SUR1) regulate insulin secretion in pancreatic beta-cells to maintain glucose homeostasis. Mutations that impair channel folding or assembly prevent cell surface expression and cause congenital hyperinsulinism. Structurally diverse K-ATP inhibitors have been shown to act as pharmacochaperones to correct mutant channel expression, but the mechanism is unknown. Here, we compare cryoEM structures of K-ATP channels bound to pharmacochaperones glibenclamide, repaglinide, and carbamazepine. CyanurBiotinDimercaptoPropionylSuccinimide (CBDPS) cross-linking mass spectrometry was used to partially confirm cryoEM structures.
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