A hydrophobic barrier deep within the inner pore of the ​TWIK-1 K2P potassium channel

Aryal, Prafulla and Abd Wahab, Firdaus and Bucci, Giovanna and Sansom, Mark and Stephen, Tucker (2014) A hydrophobic barrier deep within the inner pore of the ​TWIK-1 K2P potassium channel. Nature Communications, 5 (4377). pp. 1-9. ISSN 2041-1723

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Abstract

Recent X-ray crystal structures of the two-pore domain (K2P) family of potassium channels have revealed a unique structural architecture at the point where the cytoplasmic bundle-crossing gate is found in most other tetrameric K+ channels. However, despite the apparently open nature of the inner pore in the ​TWIK-1 ( K2P1/​KCNK1) crystal structure, the reasons underlying its low levels of functional activity remain unclear. In this study, we use a combination of molecular dynamics simulations and functional validation to demonstrate that ​TWIK-1 possesses a hydrophobic barrier deep within the inner pore, and that stochastic dewetting of this hydrophobic constriction acts as a major barrier to ion conduction. These results not only provide an important insight into the mechanisms which control ​TWIK-1 channel activity, but also have important implications for our understanding of how ion permeation may be controlled in similar ion channels and pores.

Item Type:	Article (Journal)
Additional Information:	5236/47584
Uncontrolled Keywords:	ion channel, potassium channel, two pore domain potassium channel, unclassified drug
Subjects:	Q Science > Q Science (General) R Medicine > RM Therapeutics. Pharmacology
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:	01 Mar 2016 11:25
Last Modified:	09 Jan 2018 16:49
URI:	http://irep.iium.edu.my/id/eprint/47584

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