Molecular Mechanisms of Mercury-Sensitive Aquaporins
Molecular Mechanisms of Mercury-Sensitive Aquaporins
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汞敏感水通道蛋白的分子机制
DOI：
10.1021/jacs.2c10240
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Jun Yang
中科院分区：
文献类型：
--
作者：
Huayong Xie;Shaojie Ma;Yongxiang Zhao;Hu Zhou;Qiong Tong;Yanke Chen;Zhengfeng Zhang;Kunqian Yu;Qingsong Lin;Lei Kai;Maili Liu;Jun Yang
水通道蛋白是允许水和其他小分子被动渗透穿过生物膜的跨膜通道。它们的通道活性对汞离子敏感。有趣的是，虽然大多数水通道蛋白被汞离子抑制，但一些水通道蛋白被汞离子激活。汞对水通道蛋白调控的分子基础仍然知之甚少。在此，我们研究了AQP 6抑制和激活后，结合汞离子使用固态NMR（ssNMR）和分子动力学（MD）模拟。基于分子动力学模拟和ssNMR构建的Hg-AqpZ复合物的结构，我们确定了Hg-AqpZ复合物的闭孔是由汞诱导的选择性过滤区的关键残基R189的构象变化引起的，而AQP 6的开孔是由选择性过滤区的残基H181和R196的构象变化引起的。这两种构象变化都是由于汞破坏了R189/R196的氢键网络而引起的。分子细节提供了汞介导的水通道蛋白的功能变化的结构基础。
Aquaporins are transmembrane channels that allow for the passive permeation of water and other small molecules across biological membranes. Their channel activities are sensitive to mercury ions. Intriguingly, while most aquaporins are inhibited by mercury ions, several aquaporins are activated by mercury ions. The molecular basis of the opposing aquaporin regulation by mercury remains poorly understood. Herein, we investigated AqpZ inhibition and AQP6 activation upon binding of mercury ions using solid-state NMR (ssNMR) and molecular dynamics (MD) simulations. Based on the structure of the Hg–AqpZ complex constructed by MD simulations and ssNMR, we identified that the pore closure was caused by mercury-induced conformational changes of the key residue R189 in the selectivity filter region, while pore opening was caused by conformational changes of residues H181 and R196 in the selectivity filter region in AQP6. Both conformational changes were caused by the disruption of the H-bond network of R189/R196 by mercury. The molecular details provided a structural basis for mercury-mediated functional changes in aquaporins.