Dynamic Coupling of Tyrosine 185 with the Bacteriorhodopsin Photocycle, as Revealed by Chemical Shifts, Assisted AF-QM/MM Calculations and Molecular Dynamic Simulations.

Sijin Chen,Anthony Watts,Xiaoyan Ding,Xin Zhao,Xiao He,Chao Sun

doi:10.3390/ijms222413587

Abstract

Aromatic residues are highly conserved in microbial photoreceptors and play crucial roles in the dynamic regulation of receptor functions. However, little is known about the dynamic mechanism of the functional role of those highly conserved aromatic residues during the receptor photocycle. Tyrosine 185 (Y185) is one of the highly conserved aromatic residues within the retinal binding pocket of bacteriorhodopsin (bR). In this study, we explored the molecular mechanism of its dynamic coupling with the bR photocycle by automated fragmentation quantum mechanics/molecular mechanics (AF-QM/MM) calculations and molecular dynamic (MD) simulations based on chemical shifts obtained by 2D solid-state NMR correlation experiments. We observed that Y185 plays a significant role in regulating the retinal cis–trans thermal equilibrium, stabilizing the pentagonal H-bond network, participating in the orientation switch of Schiff Base (SB) nitrogen, and opening the F42 gate by interacting with the retinal and several key residues along the proton translocation channel. Our findings provide a detailed molecular mechanism of the dynamic couplings of Y185 and the bR photocycle from a structural perspective. The method used in this paper may be applied to the study of other microbial photoreceptors.

Highlights

Bacteriorhodopsin, a microbial rhodopsin photoreceptor found in the purple membrane of Halobacterium salinarum, is a desirable system for studying the mechanism of energy transduction and ion transport in biological membranes
Our results show that Y185 plays a significant role in regulating the retinal cis–trans thermal equilibrium, stabilizing the pentagonal
This study systematically investigated the functional role of Y185 at the atomic level

Summary

Introduction

Bacteriorhodopsin (bR), a microbial rhodopsin photoreceptor found in the purple membrane of Halobacterium salinarum, is a desirable system for studying the mechanism of energy transduction and ion transport in biological membranes. It consists of seventransmembrane (7TM) helices and acts as a light-driven proton pump transporting protons against pH gradient across the membrane from the cytoplasmic side to the extracellular side [1–3]. Photoisomerization of the all-trans retinal to the 13-cis isomer induces a series of changes in the receptor to realize the transferal of a proton across the cell membrane through a photocycle including K, L, M1 , M2 , M2 ’, N, and O intermediate states [4–16].

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Conclusion