Title |
A hydrophobic barrier deep within the inner pore of the TWIK-1 K2P potassium channel
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Published in |
Nature Communications, July 2014
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DOI | 10.1038/ncomms5377 |
Pubmed ID | |
Authors |
Prafulla Aryal, Firdaus Abd-Wahab, Giovanna Bucci, Mark S. P. Sansom, Stephen J. Tucker |
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. |
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Demographic breakdown
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Student > Master | 12 | 11% |
Researcher | 11 | 10% |
Student > Doctoral Student | 9 | 8% |
Student > Bachelor | 6 | 6% |
Other | 13 | 12% |
Unknown | 20 | 19% |
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Engineering | 4 | 4% |
Other | 14 | 13% |
Unknown | 19 | 18% |