The Photocycle of Bacteriophytochrome Is Initiated by Counterclockwise Chromophore Isomerization

Photoactivation of bacteriophytochrome involves acis-trans photoisomerization of a biliverdin chromophore, butneither the precise sequence of events nor the direction of theisomerization is known. Here, we used nonadiabatic moleculardynamics simulations on the photosensory protein dimer toresolve the isomerization mechanism in atomic detail. In oursimulations the photoisomerization of the D ring occurs in thecounterclockwise direction. On a subpicosecond time scale, thephotoexcited chromophore adopts a short-lived intermediate witha highly twisted configuration stabilized by an extended hydrogen-bonding network. Within tens of picoseconds, these hydrogenbonds break, allowing the chromophore to adopt a more planarconfiguration, which we assign to the early Lumi-R state. Theisomerization process is completed via helix inversion of thebiliverdin chromophore to form the late Lumi-R state. The mechanistic insights into the photoisomerization process are essential tounderstand how bacteriophytochrome has evolved to mediate photoactivation and to engineer this protein for new applications.

Automated summary

Nonadiabatic molecular dynamics simulations were used to unravel the isomerization mechanism of bacteriophytochrome photoactivation. The simulations revealed a counterclockwise photoisomerization process accompanied by the breakage and reformation of hydrogen bonds.