A journey in the field of organic light-emitting molecules.
Design and quantum chemistry calculations within a multidisciplinary approach.
Laura Pedraza-González
Email: laura.pedraza@dcci.unipi.it
Dipartimento di Chimica e Chimica Industriale, Università di Pisa, Pisa, Italy
10:30 am – Tuesday, 22nd June 2023 (D42, Campus St. Jérôme)
In response to varying light conditions, light-harvesting complexes (LHCs) switch from a light- harvesting state to a quenched state to protect the photosynthetic organism from excessive light irradiation in a strategy known as nonphotochemical quenching (NPQ). NPQ is activated by an acidification of the thylakoid lumen, which is sensed directly or indirectly by the LHC, resulting in a conformational change of the complex that leads to the quenched state. The conformational changes responsible for NPQ activation and their connection to specific quenching mechanisms are still unknown. In this talk, I will present a multistep computational protocol to investigate the pH-triggered conformational changes in the light-harvesting complex stress-related (LHCSR) of mosses[1]. By combining constant-pH molecular dynamics[2] and enhanced sampling[3] simulations of the LHCSR1[4] protein, we find that the pH sensitivity of the complex is driven by the coupled protonation of three key residues (i.e., E114, E227 and E233) modulating the conformation of the short amphipathic helix D placed at the lumen side of the embedding membrane. Combining these results with quantum mechanics/molecular mechanics calculations, we show that the quenching mechanism sensitive to the pH goes through a charge-transfer (CT) between a carotenoid (L1-Lut) and an excited chlorophyll (aChl 612), which is controlled by the protein conformation (Figure 1).
Figure 1. pH-dependent “soft switch” for increasing/decreasing the amount of quenching in LHCSR1. (left) Conformations are explored at low pH (orange cartoons) that are not accessible at neutral pH (cyan cartoons), suggesting that a pH drop can exert a profound influence on the conformation. (right) A CT-based quenching mechanism may be tuned through conformational changes (low pH) located near helix D inducing a displacement of lutein in the site L1 toward the stroma.
References:
[1] Pedraza-González, L; Cignoni, E; D’Ascenzi, J.; Cupellini, L.; Mennucci, B. How the pH ControlsPhotoprotection in the Light-Harvesting Complex of Mosses. J. Am. Chem. Soc. 2023, 145, 13, 7482–7494
[2] Swails, J. M.; York, D. M.; Roitberg, A. E. Constant pH replica exchange molecular dynamics in explicit solvent using discrete protonation states: implementation, testing, and validation. J. Chem. Theory Comput. 2014, 10, 1341– 1352
[3] Miao, Y.; Feher, V. A.; McCammon, J. A. Gaussian Accelerated Molecular Dynamics: Unconstrained Enhanced Sampling and Free Energy Calculation. J. Chem. Theory Comput. 2015, 11, 3584– 3595
[4] Guarnetti Prandi, I.; Sláma, V.; Pecorilla, C.; Cupellini, L.; Mennucci, B. Structure of the stress-related LHCSR1 complex determined by an integrated computational strategy. Commun. Biol. 2022, 5, 1– 10
