Water transport in AQP0 aquaporin: Molecular dynamics studies
Water transport in AQP0 aquaporin: Molecular dynamics studies
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DOI：
10.1016/j.jmb.2006.04.039
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发表时间：
2006-07-07
影响因子：
5.6
通讯作者：
Jap, Bing K.
中科院分区：
文献类型：
--
作者：
Han, Bong-Gyoon;Guliaev, Anton B.;Jap, Bing K.
一个含有AQP0水通道蛋白的相反四聚体的双脂质双层结构，通过细胞外面环区域接触，最近使用电子晶体学方法获得的中分辨率图进行了建模。这些水通道的孔隙在三个区域被发现非常狭窄，随后被解释为通道的封闭状态。随后，通过x射线晶体学方法对高分辨率AQP0四聚体结构进行了测定，得到了一个孔隙模型，该模型具有EM功中提到的三种收缩中的两种以及通道孔隙中的水分子。该AQP0结构的细胞外侧收缩区明显大于基于em的模型，与高透水性AQP1相似。然而，基于x射线的AQP0研究不能确定在孔洞中发现的水分子是水从通道的一端还是两端进入的结果，也不能确定水是否可以自由地通过所有收缩点。此外，这种基于x射线的结构不能回答AQP0的双脂质双层结构是否能在功能上维持通道的不透水状态。为了解决这些问题，我们进行了分子动力学模拟，比较了脂质双层中AQP0和AQP1通道的时间依赖性行为。模拟结果表明，单或双脂质双分子层中的AQP0对水的输送并不封闭，关键侧链的热运动足以促进水通过其任何收缩区。然而，这些运动需求确实会导致显著的自由能障碍，并有助于解释AQP0气孔的透水性明显低于AQP1气孔的生理观察结果。Elsevier Ltd.出版。
A double lipid bilayer structure containing opposing tetramers of AQP0 aquaporin, in contact through extracellular face loop regions, was recently modeled using an intermediate-resolution map obtained by electron crystallographic methods. The pores of these water channels were found to be critically narrow in three regions and subsequently interpreted to be those of a closed state of the channel. The subsequent determination of a high-resolution AQP0 tetramer structure by X-ray crystallographic methods yielded a pore model featuring two of the three constrictions as noted in the EM work and water molecules within the channel pore. The extracellular-side constriction region of this AQP0 structure was significantly larger than that of the EM-based model and similar to that of the highly water permeable AQP1. The X-ray-based study of AQP0 however could not ascertain if the water molecules found in the bore were the result of water entering from one or both ends of the channel, nor whether water could freely pass through all constriction points. Additionally, this X-ray-based structure could not provide an answer to the question of whether the double lipid bilayer configuration of AQP0 Could functionally maintain a water impermeable state of the channel. To address these questions we conducted molecular dynamics simulations to compare the time-dependent behavior of the AQP0 and AQP1 channels within lipid bilayers. The simulations demonstrate that AQP0, in single or double lipid bilayers, is not closed to water transport and that thermal motions of critical side-chains are sufficient to facilitate the movement of water past any of its constriction regions. These motional requirements do however lead to significant free energy barriers and help explain physiological observations that found water permeability in AQP0 to be substantially lower than in the AQP1 pore. Published by Elsevier Ltd.