title: Theoretical Study on the UVR8 Photoreceptor: Sensing Ultraviolet-B by Tryptophan and Dissociation of Homodimer.
abstract: By the irradiation of ultraviolet-B (UV-B) light, UVR8 photoreceptor can undergo dissociation of the protein homodimer and regulate gene expression in plants. We have carried out high-level quantum mechanics (QM) and ONIOM(QM:MM) calculations and molecular dynamics (MD) simulations to study spectra of key tryptophan residues in UVR8 homodimer and to clarify the key role of important charged residues and their salt bridges as well as the feasible dissociation mechanism. First, benchmark calculations on the absorption and emission of 3-methylindole in the gas phase have been performed by different QM methods (TD-DFT, CASSCF, MS-CASPT2, and SAC-CI). Twenty different DFT functionals, including double hybrid and Minnesota functionals, were tested, but all these functionals failed to give satisfactory description of two key transitions. In comparison, SAC-CI and CASPT2 methods can give reliable transition energies and a correct order of (1)La and (1)Lb excited states. Furthermore, the vertical absorption and emission energies of tryptophan in UVR8 have been investigated by the ONIOM method. The present results suggest that W285 is the major chromophore of UVR8, while W233 can also sense the UV-B light and may be responsible for exciton coupling. Geometrical effects as well as electrostatic and polarization interactions with the protein matrix were found to influence optical properties of these tryptophan residues in UVR8. At the homodimeric interface, R286-D107 and R338-D44 salt bridges are suggested to play a crucial role for the UVR8 monomerization. In addition, the UV-B induced dissociation mechanism of the UVR8 homodimer has been proposed. The electrostatic repulsion between the partially negatively charged benzene ring of W285 in the (1)La excited state and the negatively charged D44/D107, along with electron and/or proton transfers among W285, R286 (or R338), W233 and D129, was suggested to result in the breakage of the key salt bridges, and destabilization as well as dissociation of the UVR8 dimer. The proposed mechanism also accounts for the fluorescence quenching in UVR8, and the stability and the enhanced red-shifted fluorescence in the W285F mutant.
authors.affiliation: State Key Lab of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics , Dalian 116023, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Fukui Institute for Fundamental Chemistry, Kyoto University , Kyoto 606-8103, Japan.|Department of Chemistry, South University of Science and Technology of China , Shenzhen 518055, China.
authors.forename: Lung Wa
authors.initials: LW
authors.lastname: Chung
authors.affiliation: Fukui Institute for Fundamental Chemistry, Kyoto University , Kyoto 606-8103, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Morokuma
authors.affiliation: State Key Lab of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics , Dalian 116023, China.
authors.forename: Guohui
authors.initials: G
authors.lastname: Li