ArticleMolecular cell2017
A Slow Conformational Switch in the BMAL1 Transactivation Domain Modulates Circadian Rhythms.
Article in Molecular cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 85 citations in OpenAlex.
- Circadian synchronization between diet and gut microbiota in modulating host's health.Gut microbes · 2026Review
- 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
- BMAL1 modulates glutamine supply to control haematopoietic stem and progenitor cell expansion.Development (Cambridge, England) · 2026Article
- Biochemical mechanism of the mammalian circadian clock.FEBS letters · 2026Review
- Integration of circadian and hypoxia signaling via non-canonical heterodimerization.FEBS letters · 2026Review
- Glycopolymers stabilize protein folding and protein-protein interactions via enthalpic interactions.Protein science : a publication of the Protein Society · 2026Article
- Core Circadian Protein BMAL1: Implication for Nervous System Functioning and Its Diseases.Brain sciences · 2025Review
- Tandem association of CLOCK:BMAL1 complexes on DNA enables recruitment of CBP/p300 through multivalent interactions.bioRxiv : the preprint server for biology · 2025Article
- A tethering mechanism underlies Pin1-catalyzed prolineProceedings of the National Academy of Sciences of the United States of America · 2025Article
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- ProlineJournal of the American Chemical Society · 2025Article
- Antibiofilm Activities of Tritrpticin Analogs Against PathogenicMolecules (Basel, Switzerland) · 2025Article
- Protein-adaptive differential scanning fluorimetry using conformationally responsive dyes.Nature biotechnology · 2025Article
- Temperature-dependent fold-switching mechanism of the circadian clock protein KaiB.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Structure and function of the SIT1 proline transporter in complex with the COVID-19 receptor ACE2.Nature communications · 2024Article
- Molecular switching in transcription through splicing and proline-isomerization regulates stress responses in plants.Nature communications · 2024Article
- Chaotic aging: intrinsically disordered proteins in aging-related processes.Cellular and molecular life sciences : CMLS · 2023Article
- Circadian clock regulator Bmal1 gates axon regeneration via Tet3 epigenetics in mouse sensory neurons.Nature communications · 2023Article
- FK506-Binding Protein 2 Participates in Proinsulin Folding.Biomolecules · 2023Article
- Lighting up Nobel Prize-winning studies with protein intrinsic disorder.Cellular and molecular life sciences : CMLS · 2022Review
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
The C-terminal transactivation domain (TAD) of BMAL1 (brain and muscle ARNT-like 1) is a regulatory hub for transcriptional coactivators and repressors that compete for binding and, consequently, contributes to period determination of the mammalian circadian clock. Here, we report the discovery of two distinct conformational states that slowly exchange within the dynamic TAD to control timing. This binary switch results from cis/trans isomerization about a highly conserved Trp-Pro imide bond in a region of the TAD that is required for normal circadian timekeeping. Both cis and trans isomers interact with transcriptional regulators, suggesting that isomerization could serve a role in assembling regulatory complexes in vivo. Toward this end, we show that locking the switch into the trans isomer leads to shortened circadian periods. Furthermore, isomerization is regulated by the cyclophilin family of peptidyl-prolyl isomerases, highlighting the potential for regulation of BMAL1 protein dynamics in period determination.
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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.