Structural Basis for Xenon Inhibition in a Cationic Pentameric Ligand-Gated Ion Channel.
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...
Main Authors: | , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2016-01-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC4765991?pdf=render |
id |
doaj-d0e34502d26447db9b2582079291195d |
---|---|
record_format |
Article |
spelling |
doaj-d0e34502d26447db9b2582079291195d2020-11-25T02:00:23ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01112e014979510.1371/journal.pone.0149795Structural Basis for Xenon Inhibition in a Cationic Pentameric Ligand-Gated Ion Channel.Ludovic SauguetZeineb FouratiThierry PrangéMarc DelarueNathalie Colloc'hGLIC 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.http://europepmc.org/articles/PMC4765991?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ludovic Sauguet Zeineb Fourati Thierry Prangé Marc Delarue Nathalie Colloc'h |
spellingShingle |
Ludovic Sauguet Zeineb Fourati Thierry Prangé Marc Delarue Nathalie Colloc'h Structural Basis for Xenon Inhibition in a Cationic Pentameric Ligand-Gated Ion Channel. PLoS ONE |
author_facet |
Ludovic Sauguet Zeineb Fourati Thierry Prangé Marc Delarue Nathalie Colloc'h |
author_sort |
Ludovic Sauguet |
title |
Structural Basis for Xenon Inhibition in a Cationic Pentameric Ligand-Gated Ion Channel. |
title_short |
Structural Basis for Xenon Inhibition in a Cationic Pentameric Ligand-Gated Ion Channel. |
title_full |
Structural Basis for Xenon Inhibition in a Cationic Pentameric Ligand-Gated Ion Channel. |
title_fullStr |
Structural Basis for Xenon Inhibition in a Cationic Pentameric Ligand-Gated Ion Channel. |
title_full_unstemmed |
Structural Basis for Xenon Inhibition in a Cationic Pentameric Ligand-Gated Ion Channel. |
title_sort |
structural basis for xenon inhibition in a cationic pentameric ligand-gated ion channel. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2016-01-01 |
description |
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. |
url |
http://europepmc.org/articles/PMC4765991?pdf=render |
work_keys_str_mv |
AT ludovicsauguet structuralbasisforxenoninhibitioninacationicpentamericligandgatedionchannel AT zeinebfourati structuralbasisforxenoninhibitioninacationicpentamericligandgatedionchannel AT thierryprange structuralbasisforxenoninhibitioninacationicpentamericligandgatedionchannel AT marcdelarue structuralbasisforxenoninhibitioninacationicpentamericligandgatedionchannel AT nathaliecolloch structuralbasisforxenoninhibitioninacationicpentamericligandgatedionchannel |
_version_ |
1724960989547331584 |