RESEARCH ARTICLE

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

  • Jing-Xiang Wu 1,2 ,
  • Dian Ding 1,2,3 ,
  • Mengmeng Wang 1,2,3 ,
  • Yunlu Kang 1,2 ,
  • Xin Zeng 1,2,3 ,
  • Lei Chen , 1,2
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  • 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

Received date: 06 Mar 2018

Accepted date: 14 Mar 2018

Published date: 11 Jun 2018

Copyright

2018 The Author(s) 2018

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 cryoelectron 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.

Cite this article

Jing-Xiang Wu , Dian Ding , Mengmeng Wang , Yunlu Kang , Xin Zeng , Lei Chen . Ligand binding and conformational changes of SUR1 subunit in pancreatic ATP-sensitive potassium channels[J]. Protein & Cell, 2018 , 9(6) : 553 -567 . DOI: 10.1007/s13238-018-0530-y

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