ArticleNature communications2018
An evolutionary hotspot defines functional differences between CRYPTOCHROMES.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 1 of them a synthesis that pooled it.
What it found
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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
65 citing papers in PubMed, 1 synthesis or guideline pooled it, 93 citations in OpenAlex.
- Pooled it
- Protein Surface Site Determines the Evolutionary Accessibility of Allosteric Regulation.bioRxiv : the preprint server for biology · 2026Article
- DHHC3-dependent S-Acylation of CRY1 regulates its subcellular localization and repressor function in the circadian clock.bioRxiv : the preprint server for biology · 2026Article
- A Charge-Reversal Point Mutation Completely Depletes Flavin Chromophore from European Robin Cryptochrome 4a Protein.The journal of physical chemistry letters · 2026Article
- Conserved structural motifs in PAS, LOV, and CRY proteins regulate circadian rhythms and are therapeutic targets.FEBS letters · 2026Review
- Circadian clock and cancer.Military Medical Research · 2026Review
- Structure of European robin cryptochrome 1 reveals a role in circadian rhythms, not magnetoreception.iScience · 2025Article
- Targeting Cryptochromes in Chronic Diseases.Cell biology international · 2025Review
- Tandem association of CLOCK:BMAL1 complexes on DNA enables recruitment of CBP/p300 through multivalent interactions.bioRxiv : the preprint server for biology · 2025Article
- MD Multi-Sector Selector: Recursive Extraction and Refinement of Molecular Dynamics Based Sectors Yields Two Sectors in p53 Tumor Suppressor Protein.The journal of physical chemistry. B · 2025Article
- PERspectives on circadian cell biology.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Review
- Unravelling the link between circadian clock genes and brain tumors: From pathological disruptions to potential therapeutic interventions.Frontiers in pharmacology · 2025Review
- Role of circadian clock in female embryo implantation.Frontiers in cell and developmental biology · 2025Review
- Circadian Regulation of Lipid Metabolism during Pregnancy.International journal of molecular sciences · 2024Review
- Statistical Coupling Analysis Predicts Correlated Motions in Dihydrofolate Reductase.The journal of physical chemistry. B · 2024Article
- Circadian period is compensated for repressor protein turnover rates in single cells.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Statistical Coupling Analysis Predicts Correlated Motions in Dihydrofolate Reductase.bioRxiv : the preprint server for biology · 2024Article
- A structural decryption of cryptochromes.Frontiers in chemistry · 2024Review
- Functional characterization of the CRY2 circadian clock component variant p.Ser420Phe revealed a new degradation pathway for CRY2.The Journal of biological chemistry · 2023Article
- A deazariboflavin chromophore kinetically stabilizes reduced FAD state in a bifunctional cryptochrome.Scientific reports · 2023Article
5 more citing papers are in PubMed but not listed here.
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 5 institutions in 1 country.
Funding
Abstract
Mammalian circadian clocks are driven by a transcription/translation feedback loop composed of positive regulators (CLOCK/BMAL1) and repressors (CRYPTOCHROME 1/2 (CRY1/2) and PER1/2). To understand the structural principles of regulation, we used evolutionary sequence analysis to identify co-evolving residues within the CRY/PHL protein family. Here we report the identification of an ancestral secondary cofactor-binding pocket as an interface in repressive CRYs, mediating regulation through direct interaction with CLOCK and BMAL1. Mutations weakening binding between CLOCK/BMAL1 and CRY1 lead to acceleration of the clock, suggesting that subtle sequence divergences at this site can modulate clock function. Divergence between CRY1 and CRY2 at this site results in distinct periodic output. Weaker interactions between CRY2 and CLOCK/BMAL1 at this pocket are strengthened by co-expression of PER2, suggesting that PER expression limits the length of the repressive phase in CRY2-driven rhythms. Overall, this work provides a model for the mechanism and evolutionary variation of clock regulatory mechanisms.
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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.