Allosteric Effects of the Proton Donor on the Microbial Proton Pump Proteorhodopsin
Allosteric Effects of the Proton Donor on the Microbial Proton Pump Proteorhodopsin
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DOI：
10.1016/j.bpj.2018.08.028
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发表时间：
2018-10-02
影响因子：
3.4
通讯作者：
Mertz, Blake
中科院分区：
文献类型：
--
作者：
Faramarzi, Sadegh;Feng, Jun;Mertz, Blake
变形紫红质（PR）是一种普遍存在于海洋环境中的微生物质子泵，可能在海洋碳循环中发挥重要作用。PR中视网膜发色团的光异构化导致一系列质子在特定的酸性氨基酸残基和视网膜的希夫碱之间转移，最终产生质子动力，促进ATP的合成。在类似的视网膜蛋白细菌视紫红质中，质子供体充当了一个门闩，允许大量的水流入。然而，尚不清楚PR中的质子供体E108是否利用相同的锁存机制来实现内部水化。在这里，我们使用分子动力学模拟来模拟在质子供体的质子化和去质子化状态下，PR的蓝色变体在光活化过程中的内部水化变化。我们发现，基于E108的质子化状态，PR胞质一半的内部水化水平有明显的对比。E108的去质子化不是锁存机制，而是作为一个门，利用附近的极性残基（S61）在数百纳秒内促进从细胞质到视网膜结合袋的稳定水线的形成。在微秒时间尺度上，PR没有发生大范围的构象变化。PR中质子供体去质子化效应的这种微妙而明显的差异可能有助于解释为什么涉及质子供体的光中间体（即M态和N态）具有与古细菌质子泵细菌视紫红质不同数量级的时间尺度。总的来说，我们的研究强调了理解结构波动如何导致视网膜蛋白质完成相同任务的方式的差异的重要性。
Proteorhodopsin (PR) is a microbial proton pump that is ubiquitous in marine environments and may play an important role in the oceanic carbon cycle. Photoisomerization of the retinal chromophore in PR leads to a series of proton transfers between specific acidic amino acid residues and the Schiff base of retinal, culminating in a proton motive force to facilitate ATP synthesis. The proton donor in a similar retinal protein, bacteriorhodopsin, acts as a latch to allow the influx of bulk water. However, it is unclear if the proton donor in PR, E108, utilizes the same latch mechanism to become internally hydrated. Here, we used molecular dynamics simulations to model the changes in internal hydration of the blue variant of PR during photoactivation with the proton donor in protonated and deprotonated states. We find that there is a stark contrast in the levels of internal hydration of the cytoplasmic half of PR based on the protonation state of E108. Instead of a latch mechanism, deprotonation of E108 acts as a gate, taking advantage of a nearby polar residue (S61) to promote the formation of a stable water wire from bulk cytoplasm to the retinal-binding pocket over hundreds of nanoseconds. No large-scale conformational changes occur in PR over the microsecond timescale. This subtle yet clear difference in the effect of deprotonation of the proton donor in PR may help explain why the photointermediates that involve the proton donor (i.e., M and N states) have timescales that are orders of magnitude different from the archaeal proton pump, bacteriorhodopsin. In general, our study highlights the importance of understanding how structural fluctuations lead to differences in the way that retinal proteins accomplish the same task.