Crystal structure of human aquaporin 4 at 1.8 Å and its mechanism of conductance
Crystal structure of human aquaporin 4 at 1.8 Å and its mechanism of conductance
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DOI：
10.1073/pnas.0902725106
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发表时间：
2009-05-05
影响因子：
11.1
通讯作者：
Stroud, Robert M.
中科院分区：
文献类型：
--
作者：
Ho, Joseph D.;Yeh, Ronald;Stroud, Robert M.
水通道蛋白4（AQP）是哺乳动物脑内主要的水通道，在血脑界面和脑脑脊液界面的胶质细胞中大量表达。它在脑水平衡中的功能与神经病理学疾病有关，包括脑水肿、中风和头部损伤。1.8埃的晶体结构揭示了通道的水选择性的分子基础。与水选择性AQPs AqpZ和AQP 1的结构不同，2个Asn-Pro-Ala基序的天冬酰胺不与同一个水分子氢键结合;相反，它们与通道中心的2个不同的水分子结合。进行分子动力学模拟，以询问这种观察如何影响AQP如何保持完全绝缘于任何质子传导的拟议机制，同时在整个通道中保持单个氢键水分子。
Aquaporin (AQP) 4 is the predominant water channel in the mammalian brain, abundantly expressed in the blood-brain and brain cerebrospinal fluid interfaces of glial cells. Its function in cerebral water balance has implications in neuropathological disorders, including brain edema, stroke, and head injuries. The 1.8-angstrom crystal structure reveals the molecular basis for the water selectivity of the channel. Unlike the case in the structures of water-selective AQPs AqpZ and AQP1, the asparagines of the 2 Asn-Pro-Ala motifs do not hydrogen bond to the same water molecule; instead, they bond to 2 different water molecules in the center of the channel. Molecular dynamics simulations were performed to ask how this observation bears on the proposed mechanisms for how AQPs remain totally insulating to any proton conductance while maintaining a single file of hydrogen bonded water molecules throughout the channel.