Asymmetric Connectivity Between Redox-Active Tyrosines and Reaction-Center Chlorophylls in Photosystem II

Photosystem II (PSII) contains several cofactors involved in light harvesting, charge separation, electron transfer, and catalysis. The initial charge separation in the reaction center of PSII creates the strongest known redox-cofactor oxidant in biology, a cationic radical distributed over a "special pair" of chlorophyll molecules (P680^•+). Two redox-active tyrosines, Y_Z and Y_D, located at opposite sides of the special pair, are the principal residues that reduce this cationic radical. Y_Z, in turn, oxidizes the manganese cluster of the oxygen-evolving complex to drive water oxidation, whereas Y_D forms a stable radical facilitated by local water translocation. The details of this asymmetry and the role of nearby protein residues in mediating branch-specific electron/hole-transfer pathways remain incompletely understood. Here, we investigate pathways for electron transfer (ET) from Y_Z and Y_D to P680^•+ and identify specific residues that are likely responsible for mediating ET. Graph-based analysis predicts aromatic residue-assisted pathways on both branches but also reveals a distinct tryptophan (D2-Trp191) that connects Y_D with P680^•+, whereas the corresponding D1-side position is occupied by a non-aromatic D2-Ile192. This suggests a possible role of this tryptophan as an ET mediator, thereby differentiating the nature of electronic connectivity between Y_Z/Y_D and the reaction center. Residue conservation analysis indicates retention of D2-Trp191 across various organisms. Molecular dynamics show that the predicted donor-mediator and mediator-acceptor contacts remain structurally persistent over the simulation, while QM/MM calculations show appreciable spin-density localization capacity, providing strong computational support for an ET mediator role of D2-Trp191. Together, these results suggest that ET between the redox-active tyrosines and the reaction-center chlorophylls occurs via distinct mechanisms-direct vs. mediated-with D2-Trp191 being a D2-specific mediator for the branch-selective electron/hole-transfer connectivity in PSII.