Summary of our findings and proposed models for oxidative damage and aggregation in VVD.

(A) Absorption of BL by dark-VVD results in an excited triplet state (TS). In the conventional photocycle (gray arrows) the TS decays to the flavin-cysteine adduct state corresponding to lit-VVD, from where spontaneous adduct decay follows. Alternatively (black arrows), the TS decays to the ground state by energy transfer to O₂ with the production of ¹O₂, which in turn promotes internal chemical damage. This mechanism is expected to occur in other LOV domains. In addition, we discovered that the presence of A. niger catalase (CAT) accelerates photoadduct decay. (B) The aggregation pathway of self-oxidized VVD is shown. The lit-VVD state decays into dark-VVD, followed by VVD dimerization and formation of aggregates (VVD-A) that lose the flavin cofactor. The aggregation process is under kinetic control (governed by the dynamics of the FAD-Cys adduct) and limited by VVD dimer formation. Glycerol, BSA, DTT, GSH and CAT directly interact with VVD, impeding VVD dimerization and subsequent aggregation.