Enhancing the Inhomogeneous Photodynamics of Canonical Bacteriophytochrome

Abstract

The ability of phytochromes to act as photoswitches in plants and microorganisms depends on interactions between a bilin-like chromophore and a host protein. The interconversion occurs between the spectrally distinct red (Pr) and far-red (Pfr) conformers. This conformational change is triggered by the photoisomerization of the chromophore D-ring pyrrole. In this study, as a representative example of a phytochrome-bilin system, we consider biliverdin IXα (BV) bound to bacteriophytochrome (BphP) from Deinococcus radiodurans . In the absence of light, we use an enhanced sampling molecular dynamics (MD) method to overcome the photoisomerization energy barrier. We find that the calculated free energy (FE) barriers between essential metastable states agree with spectroscopic results. We show that the enhanced dynamics of the BV chromophore in BphP contributes to triggering nanometer-scale conformational movements that propagate by two experimentally determined signal transduction pathways. Most importantly, we describe how the metastable states enable a thermal transition known as the dark reversion between Pfr and Pr, through a previously unknown intermediate state of Pfr. We present the heterogeneity of temperature-dependent Pfr states at the atomistic level. This work paves a way toward understanding the complete mechanism of the photoisomerization of a bilin-like chromophore in phytochromes.

Analogies and Differences in the Photoactivation Mechanism of Bathy and Canonical Bacteriophytochromes Revealed by Multiscale Modeling

“…This heterogeneity of Agp2 is here attributed to the dynamic nature of the protonated propionic group linked the C-ring; in fact, the second scenario rapidly coverts into the first one if we deprotonate Cprop. In DrBph, this heterogeneity was not found as Cprop is deprotonated and stabilized by strong hydrogen bonding interactions with the protein, resulting in a more rigid structure. To further support this explanation, we note that previous MD simulations performed by us on DrBph with a protonated BV revealed the presence of two basins similar to those found in this work, which were inaccessible when Cprop was deprotonated .…”

Protein control of photochemistry and transient intermediates in phytochromes

“…In particular, an a priori knowledge of how the environment affects the entire activation process is still an open question. Here, by combining excited-state surface-hopping simulations and ground-state MD simulations, we have revealed the mechanism through which the binding pocket controls both the reaction mechanism and kinetics of the photoactivation of the Pr state in DrBph 69 . In particular, the compact structure of the protein pocket forces the chromophore to proceed through a concerted rotation around two adjacent dihedrals, a mechanism known as hula-twist motion, leading to a counterclockwise rotation of the D-ring.…”

Protein control of photochemistry and transient intermediates in phytochromes

“…Here, by combining nonadiabatic and ground-state MD simulations, we have pointed to the binding pocket as a key factor controlling both the reaction mechanism and kinetics of the photoactivation of the Pr state in DrBph. 65 In particular, the compact structure of the protein pocket forces the chromophore to proceed through a concerted rotation around two adjacent dihedrals, a mechanism known as hula-twist motion, leading to a counterclockwise rotation of the D-ring. This finding seems to disagree with a previous study based on CD experiments, 66 which proposed clockwise rotation as the most probable mechanism.…”