TWIK-1 K2P钾通道内孔深处的疏水屏障。
A hydrophobic barrier deep within the inner pore of the TWIK-1 K2P potassium channel.
作者信息
Aryal Prafulla, Abd-Wahab Firdaus, Bucci Giovanna, Sansom Mark S P, Tucker Stephen J
机构信息
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.
Clarendon Laboratory, Department of Physics, University of Oxford, Oxford OX1 3PU, UK.
出版信息
Nat Commun. 2014 Jul 8;5:4377. 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.
近期钾通道双孔域（K2P）家族的X射线晶体结构显示，在大多数其他四聚体K(+)通道中存在细胞质束交叉门的位置，其具有独特的结构架构。然而，尽管在TWIK-1（K2P1/KCNK1）晶体结构中内孔表面上看似开放，但导致其功能活性水平较低的潜在原因仍不清楚。在本研究中，我们结合分子动力学模拟和功能验证，证明TWIK-1在内孔深处具有一个疏水屏障，并且这个疏水收缩处的随机去湿是离子传导的主要障碍。这些结果不仅为控制TWIK-1通道活性的机制提供了重要见解，也对我们理解类似离子通道和孔中离子渗透如何被控制具有重要意义。
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