O to bR transition in bacteriorhodopsin occurs through a proton hole mechanism.
O to bR transition in bacteriorhodopsin occurs through a proton hole mechanism.
复制标题
细菌视紫红质中的 O 到 bR 的转变是通过质子空穴机制发生的。
DOI：
10.1073/pnas.2024803118
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发表时间：
2021
影响因子：
11.1
通讯作者：
Kubař,Tomáš
中科院分区：
文献类型：
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作者：
Maag,Denis;Mast,Thilo;Elstner,Marcus;Cui,Qiang;Kubař,Tomáš
利用经典和量子力学/分子力学(QM/MM)分子动力学模拟方法，研究了细菌视紫红质(BR)中O态的结构特征及其向BR基态的转化。计算的自由能面与已有的O到Br转变的动力学和热力学实验数据是一致的。模拟结果强调了质子释放基团(PRG，由Glu194/204组成)和保守的精氨酸82在调节蛋白质腔水化水平方面的重要性。特别是，在O状态下，PRG的去质子化和Arg82的向下旋转导致水化水平升高，并形成连接PRG和质子化的Asp85的连续水网络。0.1-S的半经验QM/MM自由能模拟表明，通过这个水网络的质子交换是通过一个质子空穴的产生和传播发生的，这个空穴由ASP212传递，由Arg82稳定。这一机制为观察到细菌视紫红质D85S突变体泵入氯离子提供了解释。静电-水化耦合机理和水的所有滴定状态的参与很可能适用于许多参与生物能量传递的生物分子。
Extensive classical and quantum mechanical/molecular mechanical (QM/MM) molecular dynamics simulations are used to establish the structural features of the O state in bacteriorhodopsin (bR) and its conversion back to the bR ground state. The computed free energy surface is consistent with available experimental data for the kinetics and thermodynamics of the O to bR transition. The simulation results highlight the importance of the proton release group (PRG, consisting of Glu194/204) and the conserved arginine 82 in modulating the hydration level of the protein cavity. In particular, in the O state, deprotonation of the PRG and downward rotation of Arg82 lead to elevated hydration level and a continuous water network that connects the PRG to the protonated Asp85. Proton exchange through this water network is shown by0.1-s semiempirical QM/MM free energy simulations to occur through the generation and propagation of a proton hole, which is relayed by Asp212 and stabilized by Arg82. This mechanism provides an explanation for the observation that the D85S mutant of bacteriorhodopsin pumps chloride ions. The electrostatics–hydration coupling mechanism and the involvement of all titration states of water are likely applicable to many biomolecules involved in bioenergetic transduction.