Protein control of photochemistry and transient intermediates in phytochromes

Phytochromes are ubiquitous photoreceptors responsible for sensing light in plants, fungi and bacteria. Their photoactivation is initiated by the photoisomerization of the embedded bilin chromophore, which triggers a large conformational change in the protein. The initial photoisomerization and the following structural changes propagating from the chromophore to the entire protein are controlled by a delicate interplay of interactions between the chromophore and the protein residues. Although the numerous studies, the molecular details of this control remain elusive. Here, we apply an integrated computational approach that combines non-adiabatic and adiabatic molecular dynamics simulations to the Deinococcus radiodurans bacteriophytochrome. Our simulations show that the photoisomerization of the chromophore proceeds through a hula-twist mechanism whose kinetics is mainly determined by the hydrogen-bonding interaction of the chromophore with a close-by histidine. The resulting photoproduct rapidly relaxes in an early intermediate thanks to a stabilizing effect of a tyrosine, and finally evolves into a late intermediate, characterized by a more disordered binding pocket and a weakening of the aspartate-to-arginine salt-bridge interaction, whose cleavage is essential to interconvert the phytochrome to the final active state.