Resolving cryptic aspects of cryptochrome signaling

Zoltowski, Brian D.

doi:10.1073/pnas.1511092112

Cited by 11 publications

(6 citation statements)

References 18 publications

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“…Despite detailed study, the mechanism of signaling of At CRY2 and related CRYs, including the identity of the ground and excited states of the flavin cofactor, remains controversial 29 – 38 . In plant and animal CRYs, the ground state is proposed to be an oxidized FAD that undergoes photoreduction to an anionic semiquinone (animal CRYs) 39 or a neutral semiquinone (plant CRYs) 40 .…”

Section: Resultsmentioning

confidence: 99%

“…We hypothesize local perturbations in structure at L348/W349 sites may alter positioning of the α13-α14 turn motif and the π-cation-π interaction, ultimately perturbing the local FAD environment. However, since the signaling mechanism of cryptochromes is still under debate 35 – 38 , 45 – 47 and these residues lie in critical structural regions implicated in signal propagation, we cannot rule out the possibility that the mutations perturb structural relaxation time of the CRY2-CIB1 interaction independent of any effects on flavin redox state.…”

Section: Discussionmentioning

confidence: 99%

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Optimized second-generation CRY2–CIB dimerizers and photoactivatable Cre recombinase

et al. 2016

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Arabidopsis thaliana cryptochrome 2 (AtCRY2), a light-sensitive photosensory protein, was previously adapted for use controling protein-protein interactions through light-dependent binding to a partner protein, CIB1. While the existing CRY2/CIB dimerization system has been used extensively for optogenetic applications, some limitations exist. Here, we set out to optimize function of the CRY2/CIB system, to identify versions of CRY2/CIB that are smaller, show reduced dark interaction, and maintain longer or shorter signaling states in response to a pulse of light. We describe minimal functional CRY2 and CIB1 domains maintaining light-dependent interaction and new signaling mutations affecting AtCRY2 photocycle kinetics. The latter work implicates a α13-α14 turn motif within plant CRYs where perturbations alter signaling state lifetime. Using a long-lived L348F photocycle mutant, we engineered a second generation photoactivatable Cre recombinase, PA-Cre2.0, that shows five-fold improved dynamic range allowing robust recombination following exposure to a single, brief pulse of light.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Optimized second-generation CRY2–CIB dimerizers and photoactivatable Cre recombinase

et al. 2016

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“…Photochemically active CRYs are characterized by light-driven interconversion between redox states of the bound FAD chromophore to generate 1 of 4 spectrally distinct species: oxidized FAD (FAD ox ), 1 electron-reduced semiquinones (FAD •− or FADH • ), or the fully reduced hydroquinone (FADH − ) (6, 16). Photoreduction of FAD ox by UV-blue light is dependent on a series of Trp residues (Trp-triad or Trp-tetrad) and results in the generation of 2 candidate magnetosensitive radical pairs, M1 and M2 (Fig.…”

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confidence: 99%

Chemical and structural analysis of a photoactive vertebrate cryptochrome from pigeon

Zoltowski

Chelliah

Wickramaratne

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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104

182

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Computational and biochemical studies implicate the blue-light sensor cryptochrome (CRY) as an endogenous light-dependent magnetosensor enabling migratory birds to navigate using the Earth’s magnetic field. Validation of such a mechanism has been hampered by the absence of structures of vertebrate CRYs that have functional photochemistry. Here we present crystal structures of Columba livia (pigeon) CRY4 that reveal evolutionarily conserved modifications to a sequence of Trp residues (Trp-triad) required for CRY photoreduction. In ClCRY4, the Trp-triad chain is extended to include a fourth Trp (W369) and a Tyr (Y319) residue at the protein surface that imparts an unusually high quantum yield of photoreduction. These results are consistent with observations of night migratory behavior in animals at low light levels and could have implications for photochemical pathways allowing magnetosensing.

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“…Cryptochromes adopt a Rossman-like fold similar to photolyases [ 393 , 394 ] involved in functions ranging from DNA repair to blue light regulation of growth, development and circadian rhythms [ 395 ]. Cryptochrome photoreception is based on blue light-induced interconversion between several redox states of flavin as chromophore [ 396 ]. While the role of the tryptophan triad is controversial [ 397 ], the light-induced oligomerisation of plant cryptochrome is an accepted mechanism for light-regulation interactions with various signalling partners [ 398 , 399 , 400 ].…”

Section: Cell Signalling and Sensory Motricitymentioning

confidence: 99%

Towards the Idea of Molecular Brains

Timsit

Sergeant-Perthuis

2021

IJMS

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How can single cells without nervous systems perform complex behaviours such as habituation, associative learning and decision making, which are considered the hallmark of animals with a brain? Are there molecular systems that underlie cognitive properties equivalent to those of the brain? This review follows the development of the idea of molecular brains from Darwin’s “root brain hypothesis”, through bacterial chemotaxis, to the recent discovery of neuron-like r-protein networks in the ribosome. By combining a structural biology view with a Bayesian brain approach, this review explores the evolutionary labyrinth of information processing systems across scales. Ribosomal protein networks open a window into what were probably the earliest signalling systems to emerge before the radiation of the three kingdoms. While ribosomal networks are characterised by long-lasting interactions between their protein nodes, cell signalling networks are essentially based on transient interactions. As a corollary, while signals propagated in persistent networks may be ephemeral, networks whose interactions are transient constrain signals diffusing into the cytoplasm to be durable in time, such as post-translational modifications of proteins or second messenger synthesis. The duration and nature of the signals, in turn, implies different mechanisms for the integration of multiple signals and decision making. Evolution then reinvented networks with persistent interactions with the development of nervous systems in metazoans. Ribosomal protein networks and simple nervous systems display architectural and functional analogies whose comparison could suggest scale invariance in information processing. At the molecular level, the significant complexification of eukaryotic ribosomal protein networks is associated with a burst in the acquisition of new conserved aromatic amino acids. Knowing that aromatic residues play a critical role in allosteric receptors and channels, this observation suggests a general role of π systems and their interactions with charged amino acids in multiple signal integration and information processing. We think that these findings may provide the molecular basis for designing future computers with organic processors.

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Resolving cryptic aspects of cryptochrome signaling

Cited by 11 publications

References 18 publications

Optimized second-generation CRY2–CIB dimerizers and photoactivatable Cre recombinase

Optimized second-generation CRY2–CIB dimerizers and photoactivatable Cre recombinase

Chemical and structural analysis of a photoactive vertebrate cryptochrome from pigeon

Towards the Idea of Molecular Brains

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