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

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.
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https://hal.archives-ouvertes.fr/hal-01542985
Contributor : Carole Brunaud <>
Submitted on : Thursday, February 18, 2021 - 6:09:01 PM
Last modification on : Wednesday, February 24, 2021 - 3:09:23 AM
Long-term archiving on: : Wednesday, May 19, 2021 - 7:38:25 PM

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L Sauguet, Z Fourati, T Prangé, Marc Delarue, N Colloc'H. Structural Basis for Xenon Inhibition in a Cationic Pentameric Ligand-Gated Ion Channel. PLoS ONE, Public Library of Science, 2016, 11 (2), pp.e0149795. ⟨10.1371/journal.pone.0149795⟩. ⟨hal-01542985⟩

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