Structural Basis for Xenon Inhibition in a Cationic Pentameric Ligand-Gated Ion Channel

PLoS One. 2016 Feb 24;11(2):e0149795. doi: 10.1371/journal.pone.0149795. eCollection 2016.


GLIC receptor is a bacterial pentameric ligand-gated ion channel whose action is inhibited by xenon. Xenon has been used in clinical practice as a potent gaseous anaesthetic for decades, but the molecular mechanism of interactions with its integral membrane receptor targets remains poorly understood. Here we characterize by X-ray crystallography the xenon-binding sites within both the open and "locally-closed" (inactive) conformations of GLIC. Major binding sites of xenon, which differ between the two conformations, were identified in three distinct regions that all belong to the trans-membrane domain of GLIC: 1) in an intra-subunit cavity, 2) at the interface between adjacent subunits, and 3) in the pore. The pore site is unique to the locally-closed form where the binding of xenon effectively seals the channel. A putative mechanism of the inhibition of GLIC by xenon is proposed, which might be extended to other pentameric cationic ligand-gated ion channels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / antagonists & inhibitors*
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / metabolism
  • Crystallography, X-Ray
  • Cyanobacteria / chemistry*
  • Cyanobacteria / metabolism
  • Ion Channel Gating*
  • Ion Channels / antagonists & inhibitors*
  • Ion Channels / chemistry*
  • Ion Channels / metabolism
  • Ligands
  • Protein Binding
  • Protein Structure, Quaternary
  • Xenon / chemistry*
  • Xenon / metabolism


  • Bacterial Proteins
  • Ion Channels
  • Ligands
  • Xenon

Grant support

Zeineb Fourati-Kammoun was supported by a fellowship from Agence Nationale pour la Recherche (ANR), grant ANR 13 BSV8 0020.