ArticleProceedings of the National Academy of Sciences of the United States of America2016
Changes in active site histidine hydrogen bonding trigger cryptochrome activation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
38 citing papers in PubMed, 69 citations in OpenAlex.
- Article
- Conserved structural motifs in PAS, LOV, and CRY proteins regulate circadian rhythms and are therapeutic targets.FEBS letters · 2026Review
- Structure of European robin cryptochrome 1 reveals a role in circadian rhythms, not magnetoreception.iScience · 2025Article
- The ionic and protonation states of flavin control the activation and recovery of Drosophila cryptochrome.Communications chemistry · 2025Article
- Linear free energy relationship between reduction potential and photoreduction rate: studies on Drosophila cryptochrome.The FEBS journal · 2025Article
- Elucidation of a distinct photoreduction pathway in class IIProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Cryptochrome magnetoreception: Time course of photoactivation from non-equilibrium coarse-grained molecular dynamics.Computational and structural biotechnology journal · 2024Article
- Mitochondrial inhibitors reveal roles of specific respiratory chain complexes in CRY-dependent degradation of TIM.Scientific reports · 2024Article
- Importance of Polarizable Embedding for Absorption Spectrum Calculations ofThe journal of physical chemistry. B · 2024Article
- Loss of functionaliScience · 2024Article
- A structural decryption of cryptochromes.Frontiers in chemistry · 2024Review
- A marine cryptochrome with an inverse photo-oligomerization mechanism.Nature communications · 2023Article
- Article
- Room-temperature serial synchrotron crystallography of Drosophila cryptochrome.Acta crystallographica. Section D, Structural biology · 2022Article
- Mechanistic insight into light-dependent recognition of Timeless by Drosophila Cryptochrome.Structure (London, England : 1993) · 2022Article
- Structural and Chemical Biology Approaches Reveal Isoform-Selective Mechanisms of Ligand Interactions in Mammalian Cryptochromes.Frontiers in physiology · 2022Review
- The structural and functional roles of the flavin cofactor FAD in mammalian cryptochromes.Frontiers in molecular biosciences · 2022Review
- Cryptochromes: Photochemical and structural insight into magnetoreception.Protein science : a publication of the Protein Society · 2021Review
- Structural differences in the FAD-binding pockets and lid loops of mammalian CRY1 and CRY2 for isoform-selective regulation.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Cryptochrome expression in avian UV cones: revisiting the role of CRY1 as magnetoreceptor.Scientific reports · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Cryptochrome (CRY) is the principal light sensor of the insect circadian clock. Photoreduction of the Drosophila CRY (dCRY) flavin cofactor to the anionic semiquinone (ASQ) restructures a C-terminal tail helix (CTT) that otherwise inhibits interactions with targets that include the clock protein Timeless (TIM). All-atom molecular dynamics (MD) simulations indicate that flavin reduction destabilizes the CTT, which undergoes large-scale conformational changes (the CTT release) on short (25 ns) timescales. The CTT release correlates with the conformation and protonation state of conserved His378, which resides between the CTT and the flavin cofactor. Poisson-Boltzmann calculations indicate that flavin reduction substantially increases the His378 pKa Consistent with coupling between ASQ formation and His378 protonation, dCRY displays reduced photoreduction rates with increasing pH; however, His378Asn/Arg variants show no such pH dependence. Replica-exchange MD simulations also support CTT release mediated by changes in His378 hydrogen bonding and verify other responsive regions of the protein previously identified by proteolytic sensitivity assays. His378 dCRY variants show varying abilities to light-activate TIM and undergo self-degradation in cellular assays. Surprisingly, His378Arg/Lys variants do not degrade in light despite maintaining reactivity toward TIM, thereby implicating different conformational responses in these two functions. Thus, the dCRY photosensory mechanism involves flavin photoreduction coupled to protonation of His378, whose perturbed hydrogen-bonding pattern alters the CTT and surrounding regions.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.