Electrostatic tuning of permeation and selectivity in aquaporin water channels
Electrostatic tuning of permeation and selectivity in aquaporin water channels
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DOI：
10.1016/s0006-3495(03)74711-0
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发表时间：
2003-11-01
影响因子：
3.4
通讯作者：
Schulten, K
中科院分区：
文献类型：
--
作者：
Jensen, MO;Tajkhorshid, E;Schulten, K
用分子动力学模拟方法研究了水通道蛋白水通道家族成员--大肠杆菌甘油摄取促进剂GlpF中的水渗透和水与通道间的静电相互作用。模拟中使用了嵌入16：0/18：1C9-棕榈酰油酰磷脂酰乙醇胺膜中的四聚体模型。在模拟过程中，水分子以单列形式通过通道。单曲的动作。LE水分子通过通道是协同作用的，可以用连续时间随机游走模型来描述。在渗透过程中，单个文件的完整性保持不变，这表明破坏的水链不太可能是水通道蛋白中质子排斥的机制。渗透水与通道中心蛋白质之间的特定氢键(在两个保守的Asp-Pro-Ala“NPA”基序)，加上蛋白质静电场，在通道内强制形成双极水构型，在NPA基序上进行偶极反转。在NPA基序中，水与蛋白质的静电相互作用促进了这种转化。此外，水-水的静电相互作用在通道内的所有区域都比水-蛋白质相互作用强，除了在保守的、带正电荷的Arg残基附近。我们发现，由于保留了结构特征，通过通道的蛋白质静电场的变化完全解释了水的双极取向。尽管水分以单一的方式转运，但这种定向仍然存在。LE和阻碍质子运输。此外，我们发现对于阳离子的渗透，离子与蛋白质的静电相互作用在保守的NPA基序上比在保守的Arg基序上更不利，这表明阻止水通道蛋白质子转运的主要障碍是NPA基序。
Water permeation and electrostatic interactions between water and channel are investigated in the Escherichia coli glycerol uptake facilitator GlpF, a member of the aquaporin water channel family, by molecular dynamics simulations. A tetrameric model of the channel embedded in a 16:0/ 18:1c9-palmitoyloleylphosphatidylethanolamine membrane was used for the simulations. During the simulations, water molecules pass through the channel in single file. The movement of the single. le water molecules through the channel is concerted, and we show that it can be described by a continuous-time random-walk model. The integrity of the single file remains intact during the permeation, indicating that a disrupted water chain is unlikely to be the mechanism of proton exclusion in aquaporins. Specific hydrogen bonds between permeating water and protein at the channel center (at two conserved Asp-Pro-Ala "NPA'' motifs), together with the protein electrostatic fields enforce a bipolar water configuration inside the channel with dipole inversion at the NPA motifs. At the NPA motifs water-protein electrostatic interactions facilitate this inversion. Furthermore, water-water electrostatic interactions are in all regions inside the channel stronger than water-protein interactions, except near a conserved, positively charged Arg residue. We find that variations of the protein electrostatic field through the channel, owing to preserved structural features, completely explain the bipolar orientation of water. This orientation persists despite water translocation in single. le and blocks proton transport. Furthermore, we find that for permeation of a cation, ion-protein electrostatic interactions are more unfavorable at the conserved NPA motifs than at the conserved Arg, suggesting that the major barrier against proton transport in aquaporins is faced at the NPA motifs.