Molecular structure of the glibenclamide binding site of the beta-cell K(ATP) channel

FEBS Lett. 2001 Jun 15;499(1-2):154-60. doi: 10.1016/s0014-5793(01)02538-8.


We have investigated the structure of the glibenclamide binding site of pancreatic beta-cell ATP-sensitive potassium (K(ATP)) channels. K(ATP) channels are a complex of four pore-forming Kir6.2 subunits and four sulfonylurea receptor (SUR1) subunits. SUR1 (ABCC8) belongs to the ATP binding cassette family of proteins and has two nucleotide binding domains (NBD1 and NBD2) and 17 putative transmembrane (TM) sequences. Co-expression in a baculovirus expression system of two parts of SUR1 between NBD1 and TM12 leads to restoration of glibenclamide binding activity, whereas expression of either individual N- or C-terminal part alone gave no glibenclamide binding activity, confirming a bivalent structure of the glibenclamide binding site. By using N-terminally truncated recombinant proteins we have shown that CL3 - the cytosolic loop between TM5 and TM6 - plays a key role in formation of the N-terminal component of the glibenclamide binding site. Analysis of deletion variants of the C-terminal part of SUR1 showed that CL8 - the cytosolic loop between TM15 and TM16 - is the only determinant for the C-terminal component of the glibenclamide binding site. We suggest that in SUR1 in the native K(ATP) channel close proximity of CL3 and CL8 leads to formation of the glibenclamide binding site.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters*
  • Animals
  • Binding Sites
  • Blotting, Western
  • Cell Line
  • Cell Membrane / chemistry
  • Cell Membrane / metabolism
  • Glyburide / chemistry
  • Glyburide / metabolism*
  • Islets of Langerhans / metabolism*
  • Kinetics
  • Microscopy, Fluorescence
  • Models, Molecular
  • Potassium Channels / chemistry*
  • Potassium Channels / genetics
  • Potassium Channels / metabolism*
  • Potassium Channels, Inwardly Rectifying*
  • Protein Structure, Quaternary
  • Protein Subunits
  • Rats
  • Receptors, Drug / chemistry*
  • Receptors, Drug / genetics
  • Receptors, Drug / metabolism*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Spodoptera
  • Sulfonylurea Receptors
  • Thermodynamics


  • ATP-Binding Cassette Transporters
  • Abcc8 protein, rat
  • Potassium Channels
  • Potassium Channels, Inwardly Rectifying
  • Protein Subunits
  • Receptors, Drug
  • Recombinant Proteins
  • Sulfonylurea Receptors
  • Glyburide