Journal article
A hydrophobic barrier deep within the inner pore of the TWIK-1 K2P potassium channel
- 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.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 1.4MB, Terms of use)
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- Publisher copy:
- 10.1038/ncomms5377
Authors
- Publisher:
- Springer Nature
- Journal:
- Nature Communications More from this journal
- Volume:
- 5
- Article number:
- 4377
- Publication date:
- 2014-07-08
- Acceptance date:
- 2014-06-11
- DOI:
- EISSN:
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2041-1723
- Language:
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English
- Keywords:
- UUID:
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uuid:b289adb8-2f2b-4360-b1fc-b3443ac58363
- Local pid:
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pubs:475151
- Source identifiers:
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475151
- Deposit date:
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2014-07-26
Terms of use
- Copyright holder:
- Macmillan Publishers Limited
- Copyright date:
- 2014
- Notes:
- © 2014 Macmillan Publishers Limited. All rights reserved. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material.
- Licence:
- CC Attribution (CC BY)
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