PXD014498

PXD014498 is an original dataset announced via ProteomeXchange.

Title	Mechanism of pharmacochaperoning in ATP-sensitive potassium channels revealed by cryo-EM
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.
HostingRepository	PRIDE
AnnounceDate	2019-08-12
AnnouncementXML	Submission_2019-08-12_01:51:06.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Phillip Wilmarth
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Fusion ETD

Revision	Datetime	Status	ChangeLog Entry
0	2019-07-05 01:10:39	ID requested
⏵ 1	2019-08-12 01:51:08	announced

Martin GM, Sung MW, Yang Z, Innes LM, Kandasamy B, David LL, Yoshioka C, Shyng SL, channel revealed by cryo-EM. Elife, 8():(2019) [pubmed]

submitter keyword: pharmacological chaperones

sulfonylureas

glinides

carbamazepine

sulfonylurea receptor 1

Kir6.2

structure

Show-Ling Shyng
contact affiliation	Department of Biochemistry and Molecular Biology School of Medicine, Oregon Health & Science University 3181 SW Sam Jackson Park Road Portland, OR 97239, USA
contact email	shyngs@ohsu.edu
lab head
Phillip Wilmarth
contact affiliation	OHSU
contact email	wilmarth@ohsu.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD014498
     1. Label: PRIDE project
     2. Name: Mechanism of pharmacochaperoning in ATP-sensitive potassium channels revealed by cryo-EM