ArticleeLife2020
Dynamics at the serine loop underlie differential affinity of cryptochromes for CLOCK:BMAL1 to control circadian timing.
Article in eLife, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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.
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Who cites it
45 citing papers in PubMed, 73 citations in OpenAlex.
- Time matters: circadian genetics and the molecular logic of human health and disease.Nature reviews. Genetics · 2026Review
- The Human Circadian Clock Protein Cryptochrome-1 Responds to Photochemistry by Conformational Changes.Journal of the American Chemical Society · 2026Article
- Nuclear CK1δ as a critical determinant of PER:CRY complex dynamics and circadian period.eLife · 2026Article
- The CLOCK-BMAL1 complex in circadian regulation: structure, mechanisms, and therapeutic targeting.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Conserved structural motifs in PAS, LOV, and CRY proteins regulate circadian rhythms and are therapeutic targets.FEBS letters · 2026Review
- Disordered but rhythmic-the role of intrinsic protein disorder in eukaryotic circadian timing.FEBS letters · 2026Review
- Biochemical mechanism of the mammalian circadian clock.FEBS letters · 2026Review
- Targeting Cryptochromes in Chronic Diseases.Cell biology international · 2025Review
- A conserved chronobiological complex times C. elegans development.The EMBO journal · 2025Article
- Tandem association of CLOCK:BMAL1 complexes on DNA enables recruitment of CBP/p300 through multivalent interactions.bioRxiv : the preprint server for biology · 2025Article
- Denaturation of firefly luciferase at heat shock temperatures captured in silico.Biophysical journal · 2025Article
- CRYing for balance: a repressor lingers through peak circadian transcription.The EMBO journal · 2025Article
- PERspectives on circadian cell biology.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Review
- PAS Dimerization at the Nexus of the Mammalian Circadian Clock.Journal of molecular biology · 2024Review
- A structural decryption of cryptochromes.Frontiers in chemistry · 2024Review
- Mammalian circadian clock proteins form dynamic interacting microbodies distinct from phase separation.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Mammalian circadian clock proteins form dynamic interacting microbodies distinct from phase separation.bioRxiv : the preprint server for biology · 2023Article
- Metabolic and chemical architecture of the mammalian circadian clock.Cell chemical biology · 2023Review
- Article
- Behavioral circatidal rhythms require Bmal1 in Parhyale hawaiensis.Current biology : CB · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 7 institutions in 2 countries.
Funding
Abstract
Mammalian circadian rhythms are generated by a transcription-based feedback loop in which CLOCK:BMAL1 drives transcription of its repressors (PER1/2, CRY1/2), which ultimately interact with CLOCK:BMAL1 to close the feedback loop with ~24 hr periodicity. Here we pinpoint a key difference between CRY1 and CRY2 that underlies their differential strengths as transcriptional repressors. Both cryptochromes bind the BMAL1 transactivation domain similarly to sequester it from coactivators and repress CLOCK:BMAL1 activity. However, we find that CRY1 is recruited with much higher affinity to the PAS domain core of CLOCK:BMAL1, allowing it to serve as a stronger repressor that lengthens circadian period. We discovered a dynamic serine-rich loop adjacent to the secondary pocket in the photolyase homology region (PHR) domain that regulates differential binding of cryptochromes to the PAS domain core of CLOCK:BMAL1. Notably, binding of the co-repressor PER2 remodels the serine loop of CRY2, making it more CRY1-like and enhancing its affinity for CLOCK:BMAL1.
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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.