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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Nature Publishing Group
2014
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| Online Access: | http://irep.iium.edu.my/47584/ http://irep.iium.edu.my/47584/ http://irep.iium.edu.my/47584/ http://irep.iium.edu.my/47584/1/47584.pdf http://irep.iium.edu.my/47584/4/47584_A%20hydrophobic%20barrier%20deep_SCOPUS.pdf |
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iium-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 PeerReviewed 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 |
| repository_type |
Digital Repository |
| institution_category |
Local University |
| institution |
International Islamic University Malaysia |
| building |
IIUM Repository |
| collection |
Online Access |
| 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/ http://irep.iium.edu.my/47584/ http://irep.iium.edu.my/47584/ http://irep.iium.edu.my/47584/1/47584.pdf http://irep.iium.edu.my/47584/4/47584_A%20hydrophobic%20barrier%20deep_SCOPUS.pdf |
| first_indexed |
2023-09-18T21:07:41Z |
| last_indexed |
2023-09-18T21:07:41Z |
| _version_ |
1777411043528540160 |