Structural Determinants of Oligomerization of the Aquaporin-4 Channel.
Structural Determinants of Oligomerization of the Aquaporin-4 Channel.
复制标题
DOI：
10.1074/jbc.m115.694729
复制
发表时间：
2016-03-25
期刊：
影响因子：
--
通讯作者：
Conner AC
中科院分区：
文献类型：
--
作者：
Kitchen P;Conner MT;Bill RM;Conner AC
水通道蛋白（AQP）家族的完整膜蛋白通道介导细胞的水和溶质流动。虽然定性和定量的通道渗透性，选择性，亚细胞定位，和贩运反应已观察到不同成员的AQP家族，签名同源四聚体四级结构是保守的。使用各种生物物理技术，我们表明，突变的细胞内环（环D）的人AQP4减少寡聚化。非四聚体AQP4突变体不能重新定位到质膜响应细胞外张力的变化，尽管组成性表面表达水平和水渗透性野生型AQP4。一个网络的AQP4环D氢键相互作用，确定使用分子动力学模拟和比较的AQP 1，3和4的诱变分析的基础上，表明环D相互作用可能提供一个一般的结构框架内的AQP家族的四聚体组装。
The aquaporin (AQP) family of integral membrane protein channels mediate cellular water and solute flow. Although qualitative and quantitative differences in channel permeability, selectivity, subcellular localization, and trafficking responses have been observed for different members of the AQP family, the signature homotetrameric quaternary structure is conserved. Using a variety of biophysical techniques, we show that mutations to an intracellular loop (loop D) of human AQP4 reduce oligomerization. Non-tetrameric AQP4 mutants are unable to relocalize to the plasma membrane in response to changes in extracellular tonicity, despite equivalent constitutive surface expression levels and water permeability to wild-type AQP4. A network of AQP4 loop D hydrogen bonding interactions, identified using molecular dynamics simulations and based on a comparative mutagenic analysis of AQPs 1, 3, and 4, suggest that loop D interactions may provide a general structural framework for tetrameric assembly within the AQP family.