Structural basis for the Pr-Pfr long-range signaling mechanism of a full-length bacterial phytochrome at the atomic level

Otero, Lisandro H.; Foscaldi, Sabrina; Antelo, Giuliano T.; Rosano, Germán L.; Sirigu, Serena; Klinke, S.; Defelipe, Lucas A.; Sánchez‐Lamas, Maximiliano; Battocchio, Giovanni; Conforte, Valeria Paola; Vojnov, Adrián Alberto; Chavas, Leonard M. G.; Goldbaum, F.A.; Mroginski, Maria‐Andrea; Rinaldi, Jimena; Bonomi, Hernán Ruy

doi:10.1126/sciadv.abh1097

Cited by 18 publications

(28 citation statements)

References 83 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The sequence of events that leads to such structural changes however is still not understood, due to the multiple time and space scales involved in the process. 16,20,21,28,29,[32][33][34][35][36][37][38][39][40] Thanks to spectroscopic investigations, we know that the photocycle of bacteriophytochromes involves at least two intermediate states, namely Lumi-R and Meta-R 36,[41][42][43] . The former arises from the photoisomerization; then, on the microsecond time scale, thermal relaxation processes lead to the formation of the Meta-R intermediate.…”

Section: Introductionmentioning

confidence: 99%

Photochemistry and transient intermediates in a bacteriophytochrome photocycle revealed by multiscale simulations

Salvadori

Macaluso

Pellicci

et al. 2022

Preprint

View full text Add to dashboard Cite

Phytochromes are photoreceptors responsible for sensing light in plants, fungi and bacteria. Their photoactivation is initiated by the photoisomerization of an embedded chromophore, which triggers a large conformational change in the structure of the entire protein. Although phytochromes have been subject of numerous studies, the photoisomerization mechanism and the following reaction path leading to the final active state remain elusive. Here, we use an integrated computational approach that combines non-adiabatic surface hopping and adiabatic ground-state molecular dynamics simulations to gain atomistic details on the photoactivation mechanism of Deinococcus radiodurans bacteriophytochrome. Our simulations show that the ps-scale photoisomerization of the chromophore proceeds through a hula-twist mechanism that forces a counterclockwise rotation of the D-ring. The initial photoproduct rapidly evolves in an early intermediate which we characterize through IR spectroscopy simulation. The early intermediate then evolves on the nanosecond-to-microsecond scale to a late intermediate, characterized by a more disordered binding pocket and a clear weakening of the aspartate-to-arginine salt bridge interaction, whose cleavage is essential to interconvert to the final active state.

show abstract

Section: Introductionmentioning

confidence: 99%

Photochemistry and transient intermediates in a bacteriophytochrome photocycle revealed by multiscale simulations

Salvadori

Macaluso

Pellicci

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…This dark reversion can be considered a rare event with a specific time scale depending on the type of phytochrome ranging from minutes to hours. 33 , 59 Below, we explain how the dark reversion can be rationalized from a thermodynamical point of view.…”

Section: Resultsmentioning

confidence: 99%

“… 30 However, it has been suggested that the chromophore fluctuations are more complex when a molecular switch is embedded in the protein environment. 5 , 31 − 33 What is arguably more important, experimental results have shown a possible existence of thermally dependent states of various phytochromes, 34 likely connected to the concept of weakly coupled equilibria. 35 , 36 It is unknown how such states relate to the thermal dark reversion of Pfr to Pr at the atomistic level.…”

Section: Introductionmentioning

confidence: 99%

Enhancing the Inhomogeneous Photodynamics of Canonical Bacteriophytochrome

et al. 2022

View full text Add to dashboard Cite

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.

show abstract

“…1). Despite the numerous studies appeared so far, 13,17,18,27,28,34,[37][38][39][40][41][42][43][44] there is no consensus on the exact mechanism and the timing of the photoisomerization, neither we know the structures of the suggested intermediates and the molecular interactions that allow the propagation of the chromophore structural changes first to the binding pocket, and then to the entire protein.…”

Section: Introductionmentioning

confidence: 99%

Protein control of photochemistry and transient intermediates in phytochromes

Salvadori

Macaluso

Pellicci

et al. 2022

Preprint

View full text Add to dashboard Cite

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.

show abstract

Structural basis for the Pr-Pfr long-range signaling mechanism of a full-length bacterial phytochrome at the atomic level

Abstract: A bacterial phytochrome reversibly interconverts between a parallel and antiparallel dimeric arrangement during photoconversion.

Cited by 18 publications

References 83 publications

Photochemistry and transient intermediates in a bacteriophytochrome photocycle revealed by multiscale simulations

Photochemistry and transient intermediates in a bacteriophytochrome photocycle revealed by multiscale simulations

Enhancing the Inhomogeneous Photodynamics of Canonical Bacteriophytochrome

Protein control of photochemistry and transient intermediates in phytochromes

Contact Info

Product

Resources

About