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

作者：Aryal Prafulla; Abd Wahab Firdaus; Bucci Giovanna; Sansom Mark S P^*; Tucker Stephen J

来源：Nature Communications, 2014, 5(1): 4377.

DOI：10.1038/ncomms5377

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.

• 出版日期2014-7