Water permeation across biological membranes:: Mechanism and dynamics of aquaporin-1 and GlpF
Water permeation across biological membranes:: Mechanism and dynamics of aquaporin-1 and GlpF
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DOI：
10.1126/science.1062459
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发表时间：
2001-12-14
期刊：
影响因子：
56.9
通讯作者：
Grubmüller, H
中科院分区：
文献类型：
--
作者：
de Groot, BL;Grubmüller, H
提出了水通过人水通道蛋白-1(AQP1)和细菌甘油促进剂GlpF的“实时”分子动力学模拟。我们获得了这些高度选择性的膜通道的渗透机制的时间分辨、原子分辨模型。这两种蛋白质都起到两级过滤器的作用：保守的指纹[天冬酰胺-脯氨酸-丙氨酸(NPA)]基序形成一个选择性决定区域；第二个(芳香族/精氨酸)区域被认为是一个质子过滤器。NPA基序附近的疏水区是限速水屏障。在AQP1中，在通过过程中微调的水偶极子旋转对于水的选择性是必不可少的。在GlpF中，甘油介导的“诱导匹配”门控运动被提出以产生甘油在水中的选择性。
"Real time" molecular dynamics simulations of water permeation through human aquaporin-1 (AQP1) and the bacterial glycerol facilitator GlpF are presented. We obtained time-resolved, atomic-resolution models of the permeation mechanism across these highly selective membrane channels. Both proteins act as two-stage filters: Conserved fingerprint [asparagine-proline-alanine (NPA)] motifs form a selectivity-determining region; a second (aromatic/arginine) region is proposed to function as a proton filter. Hydrophobic regions near the NPA motifs are rate-limiting water barriers. In AQP1, a fine-tuned water dipole rotation during passage is essential for water selectivity. In GlpF, a glycerol-mediated "induced fit" gating motion is proposed to generate selectivity for glycerol over water.