Mechanism of unusual AQP6 activation by mercury binding to a pore-external residue C155.
Mechanism of unusual AQP6 activation by mercury binding to a pore-external residue C155.
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DOI：
10.1016/j.bbrc.2022.06.025
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发表时间：
2022-06
影响因子：
3.1
通讯作者：
Shaojie Ma;Huayong Xie;Kunqian Yu;Jun Yang
中科院分区：
文献类型：
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作者：
Shaojie Ma;Huayong Xie;Kunqian Yu;Jun Yang
水通道蛋白 (AQP) 将水分子运输穿过细胞膜。尽管大多数水通道蛋白被汞离子抑制，但据报道，AQP6 通过将汞离子与残基 C155 和 C190 结合而被激活。与C190和其他孔线半胱氨酸残基不同，C155位于孔外，因此不会通过与其结合的汞直接影响内部通路。汞离子与 C155 位点结合导致异常水通道激活的分子机制仍不清楚。在这里，我们通过分子动力学 (MD) 模拟研究汞离子与 C155 结合对 AQP6 的激活。 MD模拟结果表明，汞诱导的水渗透激活源自孔线残基M160的构象变化，从汞结合前的点对孔构象转变为汞结合后的远孔构象。 M160的构象变化源于α-螺旋中C155和S159之间氢键的还原，C155与汞离子的配位显着改变了它们的构象。这项研究揭示了汞离子与水通道中孔隙外部残留物结合激活水通道的复杂机制。
Aquaporins (AQPs) transport water molecules across cell membranes. Although most aquaporins are inhibited by mercury ions, AQP6 was reported to be activated by binding mercury ions to residues C155 and C190. Different from C190 and the other pore-line cysteine residues, C155 is located outside the pore, thus not directly affecting the internal pathway by mercury binding to it. The molecular mechanism of unusual water channel activation by mercury ion binding to the C155 site remains unknown. Here, we investigate the activation of AQP6 by mercury ions binding to C155 by molecular dynamics (MD) simulations. The MD simulation results show that the mercury-induced water permeation activation is derived from the conformational change of a pore-line residue M160, from a point-to-pore conformation before mercury binding to an away-pore conformation after mercury binding. The conformation change of M160 is derived from the reduction of the hydrogen bonding between C155 and S159 in the α-helix with the coordination of C155 to mercury ion altering their conformation significantly. This study reveals the complex mechanism of water channel activation by mercury ion binding to pore-external residues in water channels.