A hydrophobic barrier deep within the inner pore of the TWIK-1 K2P potassium channel.
A hydrophobic barrier deep within the inner pore of the TWIK-1 K2P potassium channel.
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DOI：
10.1038/ncomms5377
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发表时间：
2014-07-08
影响因子：
16.6
通讯作者：
Tucker, Stephen J.
中科院分区：
文献类型：
--
作者：
Aryal, Prafulla;Abd-Wahab, Firdaus;Bucci, Giovanna;Sansom, Mark S. P.;Tucker, Stephen J.
最近的X-射线晶体结构的两孔域（K2 P）家族的钾离子通道已经揭示了一个独特的结构体系的点，在细胞质的跨门被发现在大多数其他四聚体钾离子通道。然而，尽管TWIK-1（K2 P1/KCNK 1）晶体结构中的内孔具有明显的开放性质，但其低水平功能活性的原因仍不清楚。在这项研究中，我们使用的分子动力学模拟和功能验证相结合，以证明TWIK-1具有内部孔深处的疏水屏障，这种疏水收缩的随机去湿作为离子传导的主要障碍。这些结果不仅提供了一个重要的洞察机制，控制TWIK-1通道的活动，但也有重要的影响，我们了解如何离子渗透可能会控制类似的离子通道和孔。 K2 P钾通道具有与其他钾通道不同的结构。在这里，作者研究了K2 P通道TWIK-1，并表明该蛋白质含有一个深孔疏水屏障，可以阻止离子通道电导。
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. K2P potassium channels have a structure dissimilar to other potassium channels. Here, the authors study the K2P channel TWIK-1 and show that the protein contains a deep pore hydrophobic barrier that blocks ion channel conductance.
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