期刊
NATURE COMMUNICATIONS
卷 5, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms5377
关键词
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资金
- Wellcome Trust
- BBSRC
- Pfizer neusentis
- Malaysian Government
- Biotechnology and Biological Sciences Research Council [BB/L002558/1, B19456, BBS/B/16011, BB/I019855/1, BB/J00037X/1, BB/H000267/1, BEP17032] Funding Source: researchfish
- Engineering and Physical Sciences Research Council [EP/J010421/1] Funding Source: researchfish
- BBSRC [BB/I019855/1, BB/L002558/1, BB/H000267/1, BB/J00037X/1] Funding Source: UKRI
- EPSRC [EP/J010421/1] Funding Source: UKRI
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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