Structural basis of open channel block in a prokaryotic pentameric ligand-gated ion channel

Nat Struct Mol Biol. 2010 Nov;17(11):1330-6. doi: 10.1038/nsmb.1933. Epub 2010 Oct 31.


The flow of ions through cation-selective members of the pentameric ligand-gated ion channel family is inhibited by a structurally diverse class of molecules that bind to the transmembrane pore in the open state of the protein. To obtain insight into the mechanism of channel block, we have investigated the binding of positively charged inhibitors to the open channel of the bacterial homolog GLIC by using X-ray crystallography and electrophysiology. Our studies reveal the location of two regions for interactions, with larger blockers binding in the center of the membrane and divalent transition metal ions binding to the narrow intracellular pore entry. The results provide a structural foundation for understanding the interactions of the channel with inhibitors that is relevant for the entire family.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / chemistry*
  • Binding Sites
  • Cadmium / chemistry
  • Crystallography, X-Ray
  • Cyanobacteria*
  • Hydrogen-Ion Concentration
  • Ion Channel Gating
  • Lidocaine / chemistry
  • Ligand-Gated Ion Channels / chemistry*
  • Ligands
  • Membrane Transport Modulators / chemistry
  • Models, Molecular
  • Patch-Clamp Techniques
  • Quaternary Ammonium Compounds / chemistry
  • Xenopus laevis


  • Bacterial Proteins
  • Ligand-Gated Ion Channels
  • Ligands
  • Membrane Transport Modulators
  • Quaternary Ammonium Compounds
  • Cadmium
  • Lidocaine

Associated data

  • PDB/2XQ3
  • PDB/2XQ4
  • PDB/2XQ5
  • PDB/2XQ6
  • PDB/2XQ7
  • PDB/2XQ8
  • PDB/2XQ9
  • PDB/2XQA