ArticleScience (New York, N.Y.)2012
Crystal structure of the heterodimeric CLOCK:BMAL1 transcriptional activator complex.
Article in Science (New York, N.Y.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 187 papers.
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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.
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Who cites it
187 citing papers in PubMed, 350 citations in OpenAlex.
- Time matters: circadian genetics and the molecular logic of human health and disease.Nature reviews. Genetics · 2026Review
- The role of hypoxia-inducible factors in myocardial ischaemia-reperfusion injury and cardioprotection.Nature reviews. Cardiology · 2026Review
- Juvenile hormone receptor relies on conserved domain interfaces for dimerization-dependent activity.Proceedings of the National Academy of Sciences of the United States of America · 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
- Circadian clock control of breast cancer hallmarks: molecular mechanisms and therapeutic implications.Cancer metastasis reviews · 2026Review
- Small-Molecule Modulation of the Circadian Clock in Cancer and Aging.Molecules (Basel, Switzerland) · 2026Review
- Context-dependent variability of HIF heterodimers influences interactions with macromolecular and small molecule partners.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Small Molecule Regulation of CLOCK:BMAL1 DNA Binding Activity.bioRxiv : the preprint server for biology · 2026Article
- Review
- The clockwork macrophage: Timing in innate immunity.Biomedical journal · 2026Review
- Chemical biology approaches to study and target circadian clocks and their components.FEBS letters · 2026Review
- Integration of circadian and hypoxia signaling via non-canonical heterodimerization.FEBS letters · 2026Review
- Conserved structural motifs in PAS, LOV, and CRY proteins regulate circadian rhythms and are therapeutic targets.FEBS letters · 2026Review
- Biochemical mechanism of the mammalian circadian clock.FEBS letters · 2026Review
- Interplay between circadian and other transcription factors-Implications for cycling transcriptome reprogramming.FEBS letters · 2026Review
- HIF-1α and BMAL1 in bone regeneration: crosstalk between hypoxia response and circadian rhythm.Bone research · 2026Review
- Structure of European robin cryptochrome 1 reveals a role in circadian rhythms, not magnetoreception.iScience · 2025Article
- Core Circadian Protein BMAL1: Implication for Nervous System Functioning and Its Diseases.Brain sciences · 2025Review
- Circadian clock genes and insomnia: molecular mechanisms and therapeutic implications.Annals of medicine · 2025Review
- Circadian genesJournal of Zhejiang University. Science. B · 2025Review
127 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
The circadian clock in mammals is driven by an autoregulatory transcriptional feedback mechanism that takes approximately 24 hours to complete. A key component of this mechanism is a heterodimeric transcriptional activator consisting of two basic helix-loop-helix PER-ARNT-SIM (bHLH-PAS) domain protein subunits, CLOCK and BMAL1. Here, we report the crystal structure of a complex containing the mouse CLOCK:BMAL1 bHLH-PAS domains at 2.3 Å resolution. The structure reveals an unusual asymmetric heterodimer with the three domains in each of the two subunits--bHLH, PAS-A, and PAS-B--tightly intertwined and involved in dimerization interactions, resulting in three distinct protein interfaces. Mutations that perturb the observed heterodimer interfaces affect the stability and activity of the CLOCK:BMAL1 complex as well as the periodicity of the circadian oscillator. The structure of the CLOCK:BMAL1 complex is a starting point for understanding at an atomic level the mechanism driving the mammalian circadian clock.
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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.