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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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English English |
| Published: |
Nature Publishing Group
2014
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| Subjects: | |
| Online Access: | http://irep.iium.edu.my/47584/1/47584.pdf http://irep.iium.edu.my/47584/4/47584_A%20hydrophobic%20barrier%20deep_SCOPUS.pdf http://irep.iium.edu.my/47584/ http://www.nature.com/ncomms/2014/140708/ncomms5377/full/ncomms5377.html |
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| Summary: | 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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