钙调蛋白与水通道蛋白-0的非典型结合：对通道调节的影响。
Noncanonical binding of calmodulin to aquaporin-0: implications for channel regulation.
作者信息
Reichow Steve L, Gonen Tamir
机构信息
Department of Biochemistry, University of Washington, Box 357350, Seattle, WA 98195-7350, USA.
出版信息
Structure. 2008 Sep 10;16(9):1389-98. doi: 10.1016/j.str.2008.06.011.
Aquaporins (AQPs) are a family of ubiquitous membrane channels that conduct water across cell membranes. AQPs form homotetramers containing four functional and independent water pores. Aquaporin-0 (AQP0) is expressed in the eye lens, where its water permeability is regulated by calmodulin (CaM). Here we use a combination of biochemical methods and NMR spectroscopy to probe the interaction between AQP0 and CaM. We show that CaM binds the AQP0 C-terminal domain in a calcium-dependent manner. We demonstrate that only two CaM molecules bind a single AQP0 tetramer in a noncanonical fashion, suggesting a form of cooperativity between AQP0 monomers. Based on these results, we derive a structural model of the AQP0/CaM complex, which suggests CaM may be inhibitory to channel permeability by capping the vestibules of two monomers within the AQP0 tetramer. Finally, phosphorylation within AQP0's CaM binding domain inhibits the AQP0/CaM interaction, suggesting a temporal regulatory mechanism for complex formation.
水通道蛋白（AQPs）是一类广泛存在的膜通道家族，可介导水跨细胞膜转运。水通道蛋白形成含有四个功能性且独立水孔的同四聚体。水通道蛋白0（AQP0）在晶状体中表达，其水通透性受钙调蛋白（CaM）调节。在此，我们结合生化方法和核磁共振光谱来探究AQP0与CaM之间的相互作用。我们发现CaM以钙依赖的方式结合AQP0的C末端结构域。我们证明只有两个CaM分子以非典型方式结合单个AQP0四聚体，这表明AQP0单体之间存在一种协同作用形式。基于这些结果，我们推导了AQP0/CaM复合物的结构模型，该模型表明CaM可能通过封闭AQP0四聚体内两个单体的前庭来抑制通道通透性。最后，AQP0的CaM结合结构域内的磷酸化抑制了AQP0/CaM相互作用，提示了复合物形成的一种时间调节机制。
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