Dynamic mechanisms of the membrane water channel aquaporin-1 (AQP1)
Dynamic mechanisms of the membrane water channel aquaporin-1 (AQP1)
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DOI：
10.1073/pnas.251507998
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发表时间：
2001-12-04
影响因子：
11.1
通讯作者：
Ma, JP
中科院分区：
文献类型：
--
作者：
Kong, YF;Ma, JP
对水通道 aquaporin-1 的结构进行了分子动力学模拟。结果提供了水渗透中涉及的相互作用的原子描述。确定了两条主要的曲线路径。模拟证实水的选择性主要是由于尺寸排阻效应；即，最多允许一个水分子通过水通道中的狭窄狭窄处。最重要的是，与之前的建议相反，水分子与严格保守的 Asn-Pro-Ala 序列基序上的 Asn-76 和 Asn-192 极性侧链的氢键相互作用被发现对于维持狭窄收缩区域中水流的连通性至关重要。在模拟中，当 Asn-76 和 Asn-192 被近等排疏水残基取代时，水通道被完全破坏。此外，在模拟过程中，狭窄收缩的尺寸波动很大，这经常会破坏水流，从而破坏质子易位所需的单列水网络。此外，基于模拟的突变也被建议用于进一步实验研究 aquaporin-1 的水渗透机制。
Molecular-dynamics simulations were performed on the structures of the water channel aquaporin-1. The results provide an atomistic description of the interactions involved in the water permeation. Two major curvilinear pathways were identified. The simulations confirmed that the water selectivity is due primarily to the size-exclusion effect; i.e., maximally, one water molecule is allowed to pass through the narrow constriction in the aqueous pathway. Most importantly, in contrast to previous proposals, the hydrogen-bonding interactions of water molecules with the polar side chains of Asn-76 and Asn-192 on the strictly conserved Asn-Pro-Ala sequence motifs were found to be essential for maintaining the connectivity of water flow in the narrow constriction region. When Asn-76 and Asn-192 were replaced with near-isosteric hydrophobic residues in the simulation, the aqueous pathways were broken completely. Additionally, the size of the narrow constriction fluctuates significantly during the simulation, which frequently breaks the flow of water and, thus, breaks the single-file water network necessary for proton translocation. Moreover, mutations based on the simulation also have been suggested for further experimental investigation of the water-permeation mechanism of aquaporin-1.