Jing-Xiang Wu / Dian Ding / Mengmeng Wang / Yunlu Kang / Xin Zeng / Lei Chen /
PubMed Abstract
ATP-sensitive potassium channels (K) are energy sensors on the plasma membrane. By sensing the intracellular ADP/ATP ratio of β-cells, pancreatic K channels control insulin release and regulate ...ATP-sensitive potassium channels (K) are energy sensors on the plasma membrane. By sensing the intracellular ADP/ATP ratio of β-cells, pancreatic K 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 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.
EMDB-6831, PDB-5yke: Structure of pancreatic ATP-sensitive potassium channel bound with glibenclamide and ATPgammaS (focused refinement on TM at 4.11A) Method: EM (single particle) / Resolution: 4.11 Å
EMDB-6832, PDB-5ykf: Structure of pancreatic ATP-sensitive potassium channel bound with glibenclamide and ATPgammaS (3D class1 at 4.33A) Method: EM (single particle) / Resolution: 4.33 Å
EMDB-6833, PDB-5ykg: Structure of pancreatic ATP-sensitive potassium channel bound with glibenclamide and ATPgammaS (Class2 at 4.57A) Method: EM (single particle) / Resolution: 4.57 Å
EMDB-6847, PDB-5yw7: Structure of pancreatic ATP-sensitive potassium channel bound with glibenclamide and ATPgammaS (focused refinement on SUR1 ABC transporter module at 4.4A) Method: EM (single particle) / Resolution: 4.4 Å
EMDB-6848, PDB-5yw8: Structure of pancreatic ATP-sensitive potassium channel bound with ATPgammaS (all particles at 4.4A) Method: EM (single particle) / Resolution: 4.4 Å
EMDB-6850, PDB-5ywa: Structure of pancreatic ATP-sensitive potassium channel bound with ATPgammaS (CTD class 2 at 6.1A) Method: EM (single particle) / Resolution: 6.1 Å
EMDB-6851, PDB-5ywb: Structure of pancreatic ATP-sensitive potassium channel bound with Mg-ADP (CTD class2 at 5.2A) Method: EM (single particle) / Resolution: 5.2 Å
EMDB-6852, PDB-5ywc: Structure of pancreatic ATP-sensitive potassium channel bound with Mg-ADP (CTD class1 at 4.3A) Method: EM (single particle) / Resolution: 4.3 Å
EMDB-6853, PDB-5ywd: Structure of pancreatic ATP-sensitive potassium channel bound with Mg-ADP (focused refinement of SUR1 ABC transporter module at 4.22A) Method: EM (single particle) / Resolution: 4.2 Å
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