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Nat Commun. 2014 Jul 8;5:4377. doi: 10.1038/ncomms5377.

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

Author information

1
1] Clarendon Laboratory, Department of Physics, University of Oxford, Oxford OX1 3PU, UK [2] Department of Biochemistry, University of Oxford, Oxford OX1 3QX, UK [3] OXION Initiative in Ion Channels and Disease, University of Oxford, Oxford OX1 3PT, UK.
2
Clarendon Laboratory, Department of Physics, University of Oxford, Oxford OX1 3PU, UK.
3
1] Department of Biochemistry, University of Oxford, Oxford OX1 3QX, UK [2] OXION Initiative in Ion Channels and Disease, University of Oxford, Oxford OX1 3PT, UK.
4
1] Clarendon Laboratory, Department of Physics, University of Oxford, Oxford OX1 3PU, UK [2] OXION Initiative in Ion Channels and Disease, University of Oxford, Oxford OX1 3PT, UK.

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.

PMID:
25001086
PMCID:
PMC4102122
DOI:
10.1038/ncomms5377
[Indexed for MEDLINE]
Free PMC Article

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