Propensity for Proton Relay and Electrostatic Impact of Protein Reorganization in Slr1694 BLUF Photoreceptor
Propensity for Proton Relay and Electrostatic Impact of Protein Reorganization in Slr1694 BLUF Photoreceptor
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DOI：
10.1021/jacs.8b07456
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发表时间：
2018-11-14
影响因子：
15
通讯作者：
Hammes-Schiffer, Sharon
中科院分区：
文献类型：
--
作者：
Goings, Joshua J.;Reinhardt, Clorice R.;Hammes-Schiffer, Sharon
光感受器蛋白在广泛的光调节过程中起着至关重要的作用。使用黄素（BLUF）光受体的蓝光的光适应状态的形成被认为涉及光激发时氢键网络的重排。自由能模拟与部分电荷对应的相关的地面和激发态的SLR1694 BLUF域表征构象之前和之后的光激发。模拟结果表明，Trp91在化学上倾向于位于活性位点，尽管它也能够对活性位点外的构象进行采样。对于实验观察到的构象的Trp91，Gln50是ventiically有利于被定向为质子中继桥Tyr8和黄素。当Trp91被旋转，使其可以捐赠一个氢键Gln50，如在其他BLUF域中观察到的，质子中继在基态下是不受欢迎的，提供了一个可能的解释相对较快的光循环的Slr1694 BLUF域。光激发到黄素的局部激发（LE）状态诱导质子中继的形成，如果它还没有形成的话。静电嵌入的含时密度泛函理论计算表明，质子中继减少LE状态和电荷转移（CT）状态与电子转移从Tyr8黄素之间的能隙。虽然CT状态在光激发之前的能量高于LE状态，但蛋白质环境可以以稳定CT状态的方式重组，使得它低于LE状态，从而实现LE到CT状态的转变。静电分析确定运动的个别残基，如Arg65，稳定电子转移Tyr8的黄素。这些构象变化促进了BLUF光循环中关键的质子耦合电子转移反应。
Photoreceptor proteins play a vital role in a wide range of light-regulated processes. The formation of the light-adapted state of blue light using flavin (BLUF) photoreceptors is thought to involve rearrangements of hydrogen-bonding networks upon photoexcitation. Free energy simulations with partial charges corresponding to relevant ground and excited states of the Slr1694 BLUF domain characterize conformations prior to and following photoexcitation. The simulations indicate that Trp91 is thermodynamically favored to be in the active site, although it is also able to sample conformations outside the active site. For experimentally observed conformations of Trp91, Gln50 is thermodynamically favored to be oriented for a proton relay bridging Tyr8 and the flavin. When Trp91 is rotated such that it can donate a hydrogen bond to Gln50, as observed in other BLUF domains, the proton relay is not thermodynamically favored in the ground state, providing a possible explanation for the relatively fast photocycle of the Slr1694 BLUF domain. Photoexcitation to the locally excited (LE) state of the flavin induces the formation of the proton relay if it is not already formed. Electrostatically embedded time-dependent density functional theory calculations indicate that the proton relay reduces the energy gap between the LE state and the charge-transfer (CT) state associated with electron transfer from Tyr8 to the flavin. Although the CT state is higher in energy than the LE state prior to photoexcitation, the protein environment can reorganize in a manner that stabilizes the CT state so that it is lower than the LE state, enabling the LE to CT state transition. An electrostatic analysis identifies motions of individual residues, such as Arg65, that stabilize electron transfer from Tyr8 to the flavin. These conformational changes facilitate the critical proton-coupled electron transfer reaction in the BLUF photocycle.