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

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

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Abstract

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.

Item Type:	Article (Journal)
Additional Information:	5236/50082
Uncontrolled Keywords:	ion channel, potassium channel, two pore domain potassium channel, lipids, hydrophobic gating
Subjects:	Q Science > Q Science (General) Q Science > QP Physiology
Kulliyyahs/Centres/Divisions/Institutes (Can select more than one option. Press CONTROL button):	Kulliyyah of Engineering > Department of Biotechnology Engineering
Depositing User:	DR Mohd Firdaus Abd Wahab
Date Deposited:	25 Mar 2016 10:09
Last Modified:	23 May 2016 03:28
URI:	http://irep.iium.edu.my/id/eprint/50082

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