Dynamic control of slow water transport by aquaporin 0: Implications for hydration and junction stability in the eye lens
Dynamic control of slow water transport by aquaporin 0: Implications for hydration and junction stability in the eye lens
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DOI：
10.1073/pnas.0802401105
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发表时间：
2008-09-23
影响因子：
11.1
通讯作者：
Shaw, David E.
中科院分区：
文献类型：
--
作者：
Jensen, Morten O.;Dror, Ron O.;Shaw, David E.
水通道蛋白0（Aquaporin 0，AQP 0）是哺乳动物透镜纤维细胞中含量最丰富的膜蛋白，不仅是晶状体纤维细胞中主要的水通道，而且介导了晶状体纤维细胞间的薄连接。AQP 0的水渗透性明显低于其他水通道蛋白，但这种低渗透性的结构基础和生物学意义仍然不确定，正如所报道的连接形式的蛋白质的渗透性一样。为了解决这些问题，我们进行了分子动力学（MD）模拟水通过膜嵌入AQP 0在其（八聚体）交界和（四聚体）非交界的形式。从我们的模拟中，我们测量了与实验一致的非连接形式的渗透性，并发现Tyr-23和Tyr-149的保守的腔突出侧链的不同动力学调节水通道，解释了缓慢的渗透。交界和nonjunctional形式进行水等效，在以前的建议的基础上，静态晶体结构，水传导失去了交界处的形成。我们的分析表明，水通道蛋白0的低水渗透性可能有助于保持连接的机械稳定性。我们假设，导致低渗透性的结构特征可能部分地演变为允许AQP 0形成既传导水又有助于纤维细胞组织的组织结构和微循环的连接，如维持透镜的透明度所需。
Aquaporin 0 (AQP0), the most abundant membrane protein in mammalian lens fiber cells, not only serves as the primary water channel in this tissue but also appears to mediate the formation of thin junctions between fiber cells. AQP0 is remarkably less water permeable than other aquaporins, but the structural basis and biological significance of this low permeability remain uncertain, as does the permeability of the protein in a reported junctional form. To address these issues, we performed molecular dynamics (MD) simulations of water transport through membrane-embedded AQP0 in both its (octameric) junctional and (tetrameric) nonjunctional forms. From our simulations, we measured an osmotic permeability for the nonjunctional form that agrees with experiment and found that the distinct dynamics of the conserved, lumen-protruding side chains of Tyr-23 and Tyr-149 modulate water passage, accounting for the slow permeation. The junctional and nonjunctional forms conducted water equivalently, in contrast to a previous suggestion based on static crystal structures that water conduction is lost on junction formation. Our analysis suggests that the low water permeability of AQP0 may help maintain the mechanical stability of the junction. We hypothesize that the structural features leading to low permeability may have evolved in part to allow AQP0 to form junctions that both conduct water and contribute to the organizational structure of the fiber cell tissue and microcirculation within it, as required to maintain transparency of the lens.