Mechanism by which water and protein electrostatic interactions control proton transfer at the active site of channelrhodopsin.
Mechanism by which water and protein electrostatic interactions control proton transfer at the active site of channelrhodopsin.
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DOI：
10.1371/journal.pone.0201298
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Bondar AN
中科院分区：
文献类型：
--
作者：
Adam S;Bondar AN
视紫红质是光敏离子通道，其反应循环涉及质子的构象耦合转移。了解通道视紫红质的工作原理对于光遗传学的应用非常重要，这些蛋白质的光激活触发了可兴奋膜跨膜电位的变化。一个基本的开放性问题是蛋白质环境如何确保在通道的静息状态下避免从视网膜席夫碱到附近羧酸盐的非生产性质子转移。为了解决这个问题，我们进行了结合量子力学/分子力学质子转移计算与明确治疗周围的脂质膜。自由能曲线计算质子转移到counterweight，无论是通过直接跳跃或介导的水分子，表明，当视网膜是全反式，水和蛋白质的静电相互作用在很大程度上有利于质子化的视网膜席夫碱状态。我们确定了一个保守的赖氨酸基团作为一个必不可少的结构元素的质子转移能量的通道视紫红质。
Channelrhodopsins are light-sensitive ion channels whose reaction cycles involve conformation-coupled transfer of protons. Understanding how channelrhodopsins work is important for applications in optogenetics, where light activation of these proteins triggers changes in the transmembrane potential across excitable membranes. A fundamental open question is how the protein environment ensures that unproductive proton transfer from the retinal Schiff base to the nearby carboxylate counterion is avoided in the resting state of the channel. To address this question, we performed combined quantum mechanical/molecular mechanical proton transfer calculations with explicit treatment of the surrounding lipid membrane. The free energy profiles computed for proton transfer to the counterion, either via a direct jump or mediated by a water molecule, demonstrate that, when retinal is all-trans, water and protein electrostatic interactions largely favour the protonated retinal Schiff base state. We identified a conserved lysine group as an essential structural element for the proton transfer energetics in channelrhodopsins.
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影响因子：
62.1
作者：
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作者：
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