Structure of a Pancreatic ATP-Sensitive Potassium Channel

Cell. 2017 Jan 12;168(1-2):101-110.e10. doi: 10.1016/j.cell.2016.12.028. Epub 2017 Jan 12.


ATP-sensitive potassium channels (KATP) couple intracellular ATP levels with membrane excitability. These channels play crucial roles in many essential physiological processes and have been implicated extensively in a spectrum of metabolic diseases and disorders. To gain insight into the mechanism of KATP, we elucidated the structure of a hetero-octameric pancreatic KATP channel in complex with a non-competitive inhibitor glibenclamide by single-particle cryoelectron microscopy to 5.6-Å resolution. The structure shows that four SUR1 regulatory subunits locate peripherally and dock onto the central Kir6.2 channel tetramer through the SUR1 TMD0-L0 fragment. Glibenclamide-bound SUR1 uses TMD0-L0 fragment to stabilize Kir6.2 channel in a closed conformation. In another structural population, a putative co-purified phosphatidylinositol 4,5-bisphosphate (PIP2) molecule uncouples Kir6.2 from glibenclamide-bound SUR1. These structural observations suggest a molecular mechanism for KATP regulation by anti-diabetic sulfonylurea drugs, intracellular adenosine nucleotide concentrations, and PIP2 lipid.

Keywords: ABCC; K(ATP); Kir; PIP(2); SUR; glibenclamide; sulfonylurea.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / chemistry
  • ATP Binding Cassette Transporter, Subfamily B / metabolism
  • Animals
  • Cryoelectron Microscopy
  • Humans
  • Hydrolases / chemistry
  • Hydrolases / metabolism
  • KATP Channels / chemistry*
  • KATP Channels / metabolism*
  • Mammals / metabolism
  • Mesocricetus
  • Mice
  • Models, Molecular
  • Phosphoinositide Phospholipase C / chemistry
  • Phosphoinositide Phospholipase C / metabolism
  • Potassium Channels, Inwardly Rectifying / chemistry
  • Potassium Channels, Inwardly Rectifying / metabolism
  • Sulfonylurea Receptors / chemistry
  • Sulfonylurea Receptors / metabolism


  • ATP Binding Cassette Transporter, Subfamily B
  • KATP Channels
  • Kir6.2 channel
  • Potassium Channels, Inwardly Rectifying
  • Sulfonylurea Receptors
  • Hydrolases
  • Phosphoinositide Phospholipase C