Universal structure in the relaxation of photoactive proteins

Abstract

The nonequilibrium relaxation of a series of, in part, very different photoactive proteins is compared, ranging over up to eleven decades in time. The series comprises various PDZ domains and MCL 1/peptide complexes with artificial azobenzene photoswitches, as well as two different cyanobacteriochromes (Slr-g3 and TePixJ). In either case, an embedded chromophore photoisomerizes after electronic excitation on an ultrafast femtosecond to picosecond timescale, initially perturbing the structure of the protein directly around the chromophore. This local perturbation propagates over the protein in a cascade of events, which spread over a wide range of timescales from picoseconds to seconds. In a very universal manner for all protein systems, a series of kinetic steps can be identified using lifetime analysis with a roughly equidistant spacing of about one per decade on a logarithmic scale. First, the inherent resolution to disentangle exponential relaxation processes is carefully evaluated. Concluding that this is not limiting, various models are discussed that may cause such a universal relaxation response. Diffusion on a rugged free energy landscape along a one- or low-dimensional progress variable may explain that behavior, where the quasi-randomness of the kinetic matrix thins out eigenstates that contribute to transport. The separation of kinetic steps is a measure of the typical barrier heights, which, by comparison to the universal patterns observed experimentally, is found to be in the range of kBT. Such barrier heights give a protein the flexibility to quickly structurally rearrange, yet provide some level of stability, which is relevant, for example, in the context of allosteric communication.