RT Journal Article
SR Electronic
T1 Ligand binding and conformational changes of SUR1 subunit in pancreatic ATP-sensitive potassium channels
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 283440
DO 10.1101/283440
A1 Wu, Jing-Xiang
A1 Ding, Dian
A1 Wang, Mengmeng
A1 Kang, Yunlu
A1 Zeng, Xin
A1 Chen, Lei
YR 2018
UL http://biorxiv.org/content/early/2018/03/16/283440.abstract
AB 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 N-terminus participates the coupling between the peripheral SUR1 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.KATPATP-sensitive potassium channelcryo-EMcryo-electron microscopySURsulfonylurea receptorKir6inward-rectifying potassium channel 6GBMglibenclamideABCATP-binding cassettesTMD0-L0transmembrane domain 0-loop 0NBDnucleotide binding domain