中国科学院物理与数学研究所杨俊团队提出了汞敏感水通道蛋白的分子机制。相关研究成果于2022年11月22日发表在《美国化学会杂志》。

水通道蛋白允许水和其他小分子被动渗透穿过生物膜的跨膜通道。它们的通道活动对汞离子敏感。有趣的是，尽管大多数水通道蛋白被汞离子抑制，但一些水通道蛋白却被汞离子激活。汞对水通道蛋白调节的分子基础仍知之甚少。

该文中，研究人员使用固态NMR（ssNMR）和分子动力学（MD）模拟研究了汞离子结合时AqpZ的抑制和AQP6的活化。基于通过MD模拟和ssNMR构建的Hg–AqpZ复合物的结构，确定了孔隙闭合是由汞诱导的选择性过滤区中关键残基R189的构象变化引起的，而孔隙打开是由AQP6中选择性过滤区的残基H181和R196的构象变化造成的。这两种构象变化都是由汞破坏R189/R196的氢键网络引起的。分子细节为汞介导的水通道蛋白功能变化提供了结构基础。

本文通过固体核磁共振(ssNMR)和分子动力学(MD)模拟研究了汞离子结合后AqpZ的抑制和AQP6的激活。基于MD模拟和ssNMR构建的Hg-AqpZ配合物结构，研究人员确定了孔的闭合是由选择性过滤区关键残基R189的汞诱导构象变化引导的，而孔的打开是由AQP6中选择性过滤区残基H181和R196的构象变化引导的。这两种构象变化都是由汞破坏R189/R196的氢键网络引起的。这些分子细节为汞介导的水通道蛋白功能变化提供了结构基础。

附：英文原文

Title: Molecular Mechanisms of Mercury-Sensitive Aquaporins

Author: Huayong Xie, Shaojie Ma, Yongxiang Zhao, Hu Zhou, Qiong Tong, Yanke Chen, Zhengfeng Zhang, Kunqian Yu, Qingsong Lin, Lei Kai, Maili Liu, Jun Yang

Issue&Volume: November 22, 2022

Abstract: 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.

DOI: 10.1021/jacs.2c10240

Source: https://pubs.acs.org/doi/10.1021/jacs.2c10240