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

被引：110

作者：

Aryal, Prafulla ^{[1
,2
,3
]}

Abd-Wahab, Firdaus ^{[1
]}

Bucci, Giovanna ^{[1
]}

Sansom, Mark S. P. ^{[2
,3
]}

Tucker, Stephen J. ^{[1
,3
]}

机构：

[1] Univ Oxford, Dept Phys, Clarendon Lab, Oxford OX1 3PU, England

[2] Univ Oxford, Dept Biochem, Oxford OX1 3QX, England

[3] Univ Oxford, Oxford OX1 3PT, England

来源：

NATURE COMMUNICATIONS | 2014年 / 5卷

基金：

英国生物技术与生命科学研究理事会; 英国惠康基金; 英国工程与自然科学研究理事会;

关键词：

CA2+-ACTIVATED K+ CHANNELS; ION-CHANNEL; MOLECULAR-DYNAMICS; SELECTIVITY FILTER; CRYSTAL-STRUCTURE; PLASMA-MEMBRANE; WATER; CONDUCTANCE; SIMULATIONS; NANOPORES;

D O I：

10.1038/ncomms5377

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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.

引用

页数：9

共 52 条

[1]

Water dynamics and dewetting transitions in the small mechanosensitive channel MscS [J].