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Protein Cell. 2018 Jun;9(6):553-567. doi: 10.1007/s13238-018-0530-y. Epub 2018 Mar 28.

Ligand binding and conformational changes of SUR1 subunit in pancreatic ATP-sensitive potassium channels.

Wu JX1,2, Ding D1,2,3, Wang M1,2,3, Kang Y1,2, Zeng X1,2,3, Chen L4,5.

Author information

1
State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, Peking University, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Beijing, 100871, China.
2
Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, 100871, China.
3
Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China.
4
State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, Peking University, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Beijing, 100871, China. chenlei2016@pku.edu.cn.
5
Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, 100871, China. chenlei2016@pku.edu.cn.

Abstract

ATP-sensitive potassium channels (KATP) are energy sensors on the plasma membrane. By sensing the intracellular ADP/ATP ratio of β-cells, pancreatic KATP channels control insulin release and regulate metabolism at the whole body level. They are implicated in many metabolic disorders and diseases and are therefore important drug targets. Here, we present three structures of pancreatic KATP channels solved by cryo-electron microscopy (cryo-EM), at resolutions ranging from 4.1 to 4.5 Å. These structures depict the binding site of the antidiabetic drug glibenclamide, indicate how Kir6.2 (inward-rectifying potassium channel 6.2) N-terminus participates in the coupling between the peripheral SUR1 (sulfonylurea receptor 1) subunit and the central Kir6.2 channel, reveal the binding mode of activating nucleotides, and suggest the mechanism of how Mg-ADP binding on nucleotide binding domains (NBDs) drives a conformational change of the SUR1 subunit.

KEYWORDS:

ABC transporter; KATP; SUR; diabetes; glibenclamide; sulfonylurea

PMID:
29594720
PMCID:
PMC5966361
DOI:
10.1007/s13238-018-0530-y
[Indexed for MEDLINE]
Free PMC Article

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