Biochemistry Department, Oxford University, South Parks Road, Oxford, OX1 3QU, UK.
Fritz Haber Center for Molecular Dynamics Research, Institute of Chemistry, Hebrew University of Jerusalem, Jerusalem, 9190401, Israel.
Nat Commun. 2021 Jan 27;12(1):629. doi: 10.1038/s41467-020-20596-0.
Many transmembrane receptors have a desensitized state, in which they are unable to respond to external stimuli. The family of microbial rhodopsin proteins includes one such group of receptors, whose inactive or dark-adapted (DA) state is established in the prolonged absence of light. Here, we present high-resolution crystal structures of the ground (light-adapted) and DA states of Archaerhodopsin-3 (AR3), solved to 1.1 Å and 1.3 Å resolution respectively. We observe significant differences between the two states in the dynamics of water molecules that are coupled via H-bonds to the retinal Schiff Base. Supporting QM/MM calculations reveal how the DA state permits a thermodynamic equilibrium between retinal isomers to be established, and how this same change is prevented in the ground state in the absence of light. We suggest that the different arrangement of internal water networks in AR3 is responsible for the faster photocycle kinetics compared to homologs.
许多跨膜受体都有失敏状态，在这种状态下，它们无法对外界刺激做出反应。微生物视紫红质蛋白家族包括这样一组受体，其非活性或暗适应（DA）状态是在长时间没有光的情况下建立的。在这里，我们分别以 1.1Å 和 1.3Å 的分辨率呈现了地面（光适应）和 DA 状态的古菌视紫红质-3（AR3）的高分辨率晶体结构。我们观察到，在通过氢键与视黄醛 Schiff 碱偶联的水分子的动力学方面，这两种状态存在显著差异。支持的QM/MM 计算揭示了 DA 状态如何允许建立视黄醛异构体之间的热力学平衡，以及在没有光的情况下，这种相同的变化如何在基态中被阻止。我们认为，与同源物相比，AR3 中内部水网络的不同排列方式负责更快的光循环动力学。
