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

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 por...

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Main Authors: Aryal, Prafulla, Abd Wahab, Firdaus, Bucci, Giovanna, Sansom, Mark, Stephen, Tucker
Format: Article
Language:English
English
Published: Nature Publishing Group 2014
Subjects:
Q Science (General)
RM Therapeutics. Pharmacology
Online Access:http://irep.iium.edu.my/47584/1/47584.pdf
http://irep.iium.edu.my/47584/4/47584_A%20hydrophobic%20barrier%20deep_SCOPUS.pdf
http://irep.iium.edu.my/47584/
http://www.nature.com/ncomms/2014/140708/ncomms5377/full/ncomms5377.html
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spelling my.iium.irep.475842018-01-09T08:49:47Z http://irep.iium.edu.my/47584/ A hydrophobic barrier deep within the inner pore of the ​TWIK-1 K2P potassium channel Aryal, Prafulla Abd Wahab, Firdaus Bucci, Giovanna Sansom, Mark Stephen, Tucker Q Science (General) RM Therapeutics. Pharmacology 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. Nature Publishing Group 2014-07-08 Article REM application/pdf en http://irep.iium.edu.my/47584/1/47584.pdf application/pdf en http://irep.iium.edu.my/47584/4/47584_A%20hydrophobic%20barrier%20deep_SCOPUS.pdf 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 http://www.nature.com/ncomms/2014/140708/ncomms5377/full/ncomms5377.html 10.1038/ncomms5377
institution Universiti Islam Antarabangsa Malaysia
building IIUM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider International Islamic University Malaysia
content_source IIUM Repository (IREP)
url_provider http://irep.iium.edu.my/
language English
English
topic Q Science (General)
RM Therapeutics. Pharmacology
spellingShingle Q Science (General)
RM Therapeutics. Pharmacology
Aryal, Prafulla
Abd Wahab, Firdaus
Bucci, Giovanna
Sansom, Mark
Stephen, Tucker
A hydrophobic barrier deep within the inner pore of the ​TWIK-1 K2P potassium channel
description 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.
format Article
author Aryal, Prafulla
Abd Wahab, Firdaus
Bucci, Giovanna
Sansom, Mark
Stephen, Tucker
author_facet Aryal, Prafulla
Abd Wahab, Firdaus
Bucci, Giovanna
Sansom, Mark
Stephen, Tucker
author_sort Aryal, Prafulla
title A hydrophobic barrier deep within the inner pore of the ​TWIK-1 K2P potassium channel
title_short A hydrophobic barrier deep within the inner pore of the ​TWIK-1 K2P potassium channel
title_full A hydrophobic barrier deep within the inner pore of the ​TWIK-1 K2P potassium channel
title_fullStr A hydrophobic barrier deep within the inner pore of the ​TWIK-1 K2P potassium channel
title_full_unstemmed A hydrophobic barrier deep within the inner pore of the ​TWIK-1 K2P potassium channel
title_sort hydrophobic barrier deep within the inner pore of the ​twik-1 k2p potassium channel
publisher Nature Publishing Group
publishDate 2014
url http://irep.iium.edu.my/47584/1/47584.pdf
http://irep.iium.edu.my/47584/4/47584_A%20hydrophobic%20barrier%20deep_SCOPUS.pdf
http://irep.iium.edu.my/47584/
http://www.nature.com/ncomms/2014/140708/ncomms5377/full/ncomms5377.html
_version_ 1643613219812540416
score 13.211869

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