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

• Published in: Protein & cell Vol. 9; no. 6; pp. 553 - 567
• Main Authors: Wu, Jing-Xiang, Ding, Dian, Wang, Mengmeng, Kang, Yunlu, Zeng, Xin, Chen, Lei
• Format: Journal Article
• Language: English
• Published: Beijing Higher Education Press 01.06.2018; Springer Nature B.V; Oxford University Press
• Subjects: ABC transporter; Binding sites; Biochemistry; Biomedical and Life Sciences; Cell Biology; Developmental Biology; diabetes; Diabetes mellitus; Electron microscopy; Glibenclamide; Human Genetics; Insulin; K ATP; KATP; Life Sciences; Metabolic disorders; N-Terminus; Nucleotides; Pancreas; Potassium; Potassium channels; Potassium channels (inwardly-rectifying); Protein Science; Research Article; Stem Cells; Sulfonylurea; SUR; SUR; sulfonylurea; K; ABC transporter; glibenclamide; diabetes; KATP
• ISSN: 1674-800X; 1674-8018
• DOI: 10.1007/s13238-018-0530-y

ATP-sensitive potassium channels (K ATP) are energy sensors on the plasma membrane. By sensing the intracellular ADP/ATP ratio of β-cells, pancreatic K ATP 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 K ATP 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.