Influence of lipids on the hydrophobic barrier within the pore of the TWIK-1 K2P channel.
Influence of lipids on the hydrophobic barrier within the pore of the TWIK-1 K2P channel.
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DOI：
10.4161/19336950.2014.981987
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Tucker SJ
中科院分区：
文献类型：
--
作者：
Aryal P;Abd-Wahab F;Bucci G;Sansom MS;Tucker SJ
最近的几个离子通道结构在它们的跨膜螺旋之间的界面上显示出了大的侧门，或“开窗”，可能将离子传导途径暴露在双分子层的脂质核心上。在最近的一项研究中，我们证明了TWIK-1 K2P通道的功能活性受到内孔深处疏水残基存在的影响。这些残基位于TWIK-1结构的开孔附近，通过形成离子传导的疏水屏障来促进孔的脱湿。在我们之前的MD模拟中，脂质尾部被观察到进入这些孔。在该研究的附录中，我们研究了脂质对脱湿过程的贡献。我们的研究结果表明，来自上下小叶的脂质尾部都可以占据气孔并部分渗透到气孔中。脂质尾不会在空间上阻塞孔，但疏水屏障内的水与孔内壁内脂质尾的数量呈反比关系。然而，脱湿仍然发生在没有脂尾的情况下，孔隙水化似乎主要由排列在孔腔最窄部分的侧链决定。
Several recent ion channel structures have revealed large side portals, or ‘fenestrations’ at the interface between their transmembrane helices that potentially expose the ion conduction pathway to the lipid core of the bilayer. In a recent study we demonstrated that functional activity of the TWIK-1 K2P channel is influenced by the presence of hydrophobic residues deep within the inner pore. These residues are located near the fenestrations in the TWIK-1 structure and promote dewetting of the pore by forming a hydrophobic barrier to ion conduction. During our previous MD simulations, lipid tails were observed to enter these fenestrations. In this addendum to that study, we investigate lipid contribution to the dewetting process. Our results demonstrate that lipid tails from both the upper and lower leaflets can occupy the fenestrations and partially penetrate into the pore. The lipid tails do not sterically occlude the pore, but there is an inverse correlation between the presence of water within the hydrophobic barrier and the number of lipids tails within the lining of the pore. However, dewetting still occurs in the absence of lipids tails, and pore hydration appears to be determined primarily by those side-chains lining the narrowest part of the pore cavity.