The channel architecture of aquaporin 0 at a 2.2-Å resolution
The channel architecture of aquaporin 0 at a 2.2-Å resolution
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DOI：
10.1073/pnas.0405274101
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发表时间：
2004-09-28
影响因子：
11.1
通讯作者：
Stroud, RM
中科院分区：
文献类型：
--
作者：
Harries, WEC;Akhavan, D;Stroud, RM
我们确定了牛水通道蛋白 0 (AQP0) 的 X 射线结构，分辨率为 2.2 埃。这种真核完整膜蛋白的结构表明，AQP0 对水运输的选择性基于特征氨基酸残基的身份和位置，这些氨基酸残基是 AQP 蛋白家族水选择性臂的标志。此外，通道管腔仅因两条准2倍相关的酪氨酸侧链而变窄，这可能是相对于其他AQP水导率降低的原因。该通道在功能上对水的通道开放，因为通道内有八个离散的水分子。将此结构与最近在 pH 6.0 下被解释为闭合的羊 AQP0 连接形式的电子衍射结构进行比较，表明 AQP0 结构没有整体变化，侧链位置只有很小的变化。我们观察到在 pH 10 时通道或整个分子没有结构变化，这可以解释为在 pH > 6.5 时 AQP0 介导的水运输的假定 pH 门控机制。与电子衍射结构相反，比较显示没有证据表明 pH 6.0 时 AQP0 胞外结构域的联合诱导了通道门控。我们的结构有助于分析细胞外结构域的相互作用以及 AQP0 细胞间粘附作用的可能性。此外，我们的结构说明了由于突变而形成某些类型白内障的基础。
We determined the x-ray structure of bovine aquaporin 0 (AQP0) to a resolution of 2.2 Angstrom. The structure of this eukaryotic, integral membrane protein suggests that the selectivity of AQP0 for water transport is based on the identity and location of signature amino acid residues that are hallmarks of the water-selective arm of the AQP family of proteins. Furthermore, the channel lumen is narrowed only by two, quasi-2-fold related tyrosine side chains that might account for reduced water conductance relative to other AQPs. The channel is functionally open to the passage of water because there are eight discreet water molecules within the channel. Comparison of this structure with the recent electron-diffraction structure of the junctional form of sheep AQP0 at pH 6.0 that was interpreted as closed shows no global change in the structure of AQP0 and only small changes in side-chain positions. We observed no structural change to the channel or the molecule as a whole at pH 10, which could be interpreted as the postulated pH-gating mechanism of AQP0-mediated water transport at pH >6.5. Contrary to the electron-diffraction structure, the comparison shows no evidence of channel gating induced by association of the extracellular domains of AQP0 at pH 6.0. Our structure aids the analysis of the interaction of the extracellular domains and the possibility of a cell-cell adhesion role for AQP0. In addition, our structure illustrates the basis for formation of certain types of cataracts that are the result of mutations.