High-resolution structures of the M2 channel from influenza A virus reveal dynamic pathways for proton stabilization and transduction
High-resolution structures of the M2 channel from influenza A virus reveal dynamic pathways for proton stabilization and transduction
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DOI：
10.1073/pnas.1518493112
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发表时间：
2015-11-17
影响因子：
11.1
通讯作者：
DeGrado, William F.
中科院分区：
文献类型：
--
作者：
Thomaston, Jessica L.;Alfonso-Prieto, Mercedes;DeGrado, William F.
来自甲型流感病毒的基质2（M2）蛋白是使用His37作为选择性过滤器的质子通道。在这里，我们报告的高分辨率（1.10埃）的M2的跨膜结构域在低和高pH值的低温晶体结构。这些结构表明，沃茨孔内形成氢键网络或“水线”跨越17埃的通道入口His37。孔内衬羰基位于通过第二壳层相互作用，包括桥接水分子稳定水合氢离子。此外，室温晶体结构表明，尽管静电场较高，但随着温度升高和pH值降低，水变得越来越流动。互补的分子动力学模拟揭示了一个集体开关的氢键取向，可以有助于质子通量的方向性，因为His37是动态质子化和去质子化的传导周期。
The matrix 2 (M2) protein from influenza A virus is a proton channel that uses His37 as a selectivity filter. Here we report high-resolution (1.10 angstrom) cryogenic crystallographic structures of the transmembrane domain of M2 at low and high pH. These structures reveal that waters within the pore form hydrogen-bonded networks or "water wires" spanning 17 angstrom from the channel entrance to His37. Pore-lining carbonyl groups are well situated to stabilize hydronium via second-shell interactions involving bridging water molecules. In addition, room temperature crystallographic structures indicate that water becomes increasingly fluid with increasing temperature and decreasing pH, despite the higher electrostatic field. Complementary molecular dynamics simulations reveal a collective switch of hydrogen bond orientations that can contribute to the directionality of proton flux as His37 is dynamically protonated and deprotonated in the conduction cycle.