Influence of lipids on the hydrophobic barrier within the pore of the TWIK-1 K2P channel

Several recent ion channel structures have revealed large side portals, or ‘fenestrations’ at the interface between their transmembrane helices that potentially expose the ion conduction pathway to the lipid core of the bilayer. In a recent study we demonstrated that functional activity of the TWIK-...

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Main Authors:	Aryal, Prafulla, Abd. Wahab, Mohd. Firdaus, Bucci, Giovanna, Sansom, Mark S.P., Tucker, Stephen J.
Format:	Article
Language:	English
Published:	Taylor and Francis Group, LLC 2015
Subjects:	Q Science (General) QP Physiology
Online Access:	http://irep.iium.edu.my/50082/ http://irep.iium.edu.my/50082/ http://irep.iium.edu.my/50082/ http://irep.iium.edu.my/50082/1/50082.pdf

id	iium-50082
recordtype	eprints
spelling	iium-500822016-05-22T19:28:58Z http://irep.iium.edu.my/50082/ Influence of lipids on the hydrophobic barrier within the pore of the TWIK-1 K2P channel Aryal, Prafulla Abd. Wahab, Mohd. Firdaus Bucci, Giovanna Sansom, Mark S.P. Tucker, Stephen J. Q Science (General) QP Physiology Several recent ion channel structures have revealed large side portals, or ‘fenestrations’ at the interface between their transmembrane helices that potentially expose the ion conduction pathway to the lipid core of the bilayer. In a recent study we demonstrated that functional activity of the TWIK-1 K2P channel is influenced by the presence of hydrophobic residues deep within the inner pore. These residues are located near the fenestrations in the TWIK-1 structure and promote dewetting of the pore by forming a hydrophobic barrier to ion conduction. During our previous MD simulations, lipid tails were observed to enter these fenestrations. In this addendum to that study, we investigate lipid contribution to the dewetting process. Our results demonstrate that lipid tails from both the upper and lower leaflets can occupy the fenestrations and partially penetrate into the pore. The lipid tails do not sterically occlude the pore, but there is an inverse correlation between the presence of water within the hydrophobic barrier and the number of lipids tails within the lining of the pore. However, dewetting still occurs in the absence of lipids tails, and pore hydration appears to be determined primarily by those side-chains lining the narrowest part of the pore cavity. Taylor and Francis Group, LLC 2015-01 Article PeerReviewed application/pdf en http://irep.iium.edu.my/50082/1/50082.pdf Aryal, Prafulla and Abd. Wahab, Mohd. Firdaus and Bucci, Giovanna and Sansom, Mark S.P. and Tucker, Stephen J. (2015) Influence of lipids on the hydrophobic barrier within the pore of the TWIK-1 K2P channel. Channels, 9 (1). pp. 44-49. ISSN 1933-6950 E-ISSN 1933-6969 http://www.tandfonline.com/doi/full/10.4161/19336950.2014.981987 10.4161/19336950.2014.981987
repository_type	Digital Repository
institution_category	Local University
institution	International Islamic University Malaysia
building	IIUM Repository
collection	Online Access
language	English
topic	Q Science (General) QP Physiology
spellingShingle	Q Science (General) QP Physiology Aryal, Prafulla Abd. Wahab, Mohd. Firdaus Bucci, Giovanna Sansom, Mark S.P. Tucker, Stephen J. Influence of lipids on the hydrophobic barrier within the pore of the TWIK-1 K2P channel
description	Several recent ion channel structures have revealed large side portals, or ‘fenestrations’ at the interface between their transmembrane helices that potentially expose the ion conduction pathway to the lipid core of the bilayer. In a recent study we demonstrated that functional activity of the TWIK-1 K2P channel is influenced by the presence of hydrophobic residues deep within the inner pore. These residues are located near the fenestrations in the TWIK-1 structure and promote dewetting of the pore by forming a hydrophobic barrier to ion conduction. During our previous MD simulations, lipid tails were observed to enter these fenestrations. In this addendum to that study, we investigate lipid contribution to the dewetting process. Our results demonstrate that lipid tails from both the upper and lower leaflets can occupy the fenestrations and partially penetrate into the pore. The lipid tails do not sterically occlude the pore, but there is an inverse correlation between the presence of water within the hydrophobic barrier and the number of lipids tails within the lining of the pore. However, dewetting still occurs in the absence of lipids tails, and pore hydration appears to be determined primarily by those side-chains lining the narrowest part of the pore cavity.
format	Article
author	Aryal, Prafulla Abd. Wahab, Mohd. Firdaus Bucci, Giovanna Sansom, Mark S.P. Tucker, Stephen J.
author_facet	Aryal, Prafulla Abd. Wahab, Mohd. Firdaus Bucci, Giovanna Sansom, Mark S.P. Tucker, Stephen J.
author_sort	Aryal, Prafulla
title	Influence of lipids on the hydrophobic barrier within the pore of the TWIK-1 K2P channel
title_short	Influence of lipids on the hydrophobic barrier within the pore of the TWIK-1 K2P channel
title_full	Influence of lipids on the hydrophobic barrier within the pore of the TWIK-1 K2P channel
title_fullStr	Influence of lipids on the hydrophobic barrier within the pore of the TWIK-1 K2P channel
title_full_unstemmed	Influence of lipids on the hydrophobic barrier within the pore of the TWIK-1 K2P channel
title_sort	influence of lipids on the hydrophobic barrier within the pore of the twik-1 k2p channel
publisher	Taylor and Francis Group, LLC
publishDate	2015
url	http://irep.iium.edu.my/50082/ http://irep.iium.edu.my/50082/ http://irep.iium.edu.my/50082/ http://irep.iium.edu.my/50082/1/50082.pdf
first_indexed	2023-09-18T21:10:46Z
last_indexed	2023-09-18T21:10:46Z
_version_	1777411236894343168

Influence of lipids on the hydrophobic barrier within the pore of the TWIK-1 K2P channel

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