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

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

Author information

1
Unité de Dynamique Structurale des Macromolécules (UMR 3528 CNRS) Institut Pasteur, Paris, France.
2
Laboratoire de cristallographie et RMN biologiques (UMR 8015 CNRS), Paris, France.
3
CNRS, UMR 6301, ISTCT CERVOxy group, GIP Cyceron, Caen, France.
4
UNICAEN, Normandie Univ., UMR 6301 ISTCT, Caen, France.
5
CEA, DSV/I2BM, UMR 6301 ISTCT, Caen, France.

Abstract

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.

PMID:
26910105
PMCID:
PMC4765991
DOI:
10.1371/journal.pone.0149795
[Indexed for MEDLINE]
Free PMC Article

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