Volume 9 Issue 6
Jun.  2018
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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
Citation: 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

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

doi: 10.1007/s13238-018-0530-y
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The work is supported by grants from the Ministry of Science and Technology of China (National Key R&D Program of China, 2016YFA0502004 to Lei Chen) and National Natural Science Foundation of China (Grant Nos. 31622021 and 31521062 to Lei Chen) and Young Thousand Talents Program of China to Lei Chen and the China Postdoctoral Science Foundation (2016M600856 and 2017T100014 to Jing-Xiang Wu). Jing-Xiang Wu is supported by the postdoctoral foundation of the Peking-Tsinghua Center for Life Sciences, Peking University.

  • Received Date: 2018-03-06
  • Rev Recd Date: 2018-03-14
  • 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.
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