ArticleThe Journal of biological chemistry2011
Thiol-disulfide redox dependence of heme binding and heme ligand switching in nuclear hormone receptor rev-erb{beta}.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 96 citations in OpenAlex.
- Heme and CO metabolism by the canonical human heme oxygenases.Journal of inorganic biochemistry · 2026Review
- Spectroscopic Interrogation of Thiolate Hydrogen Bonding in the CO Sensor Protein CooA: Implications for Thiolate Ligation Stability and Cytochrome P450 Function.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- Mitochondrial inhibitors reveal roles of specific respiratory chain complexes in CRY-dependent degradation of TIM.Scientific reports · 2024Article
- Analytical Methods for Assessing Thiol Antioxidants in Biological Fluids: A Review.Molecules (Basel, Switzerland) · 2024Review
- Unraveling the Interplay of Dopamine, Carbon Monoxide, and Heme Oxygenase in Neuromodulation and Cognition.ACS chemical neuroscience · 2024Review
- Coupling allows robust mammalian redox circadian rhythms despite heterogeneity and noise.Heliyon · 2024Article
- Oxidative stress in retinal pigment epithelium degeneration: from pathogenesis to therapeutic targets in dry age-related macular degeneration.Neural regeneration research · 2023Review
- Article
- Perfecting the Life Clock: The Journey from PTO to TTFL.International journal of molecular sciences · 2023Review
- Mitochondrial COA7 is a heme-binding protein with disulfide reductase activity, which acts in the early stages of complex IV assembly.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Regulation of protein function and degradation by heme, heme responsive motifs, and CO.Critical reviews in biochemistry and molecular biology · 2022Review
- Circadian Regulation and Clock-Controlled Mechanisms of Glycerophospholipid Metabolism from Neuronal Cells and Tissues to Fibroblasts.Molecular neurobiology · 2022Review
- Review
- Diurnal changes in perineuronal nets and parvalbumin neurons in the rat medial prefrontal cortex.Brain structure & function · 2021Article
- Article
- Ferric heme as a CO/NO sensor in the nuclear receptor Rev-Erbß by coupling gas binding to electron transfer.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Transcriptional Control of Circadian Rhythms and Metabolism: A Matter of Time and Space.Endocrine reviews · 2020Review
- Discovery of a heme-binding domain in a neuronal voltage-gated potassium channel.The Journal of biological chemistry · 2020Article
- A Heme Propionate Staples the Structure of CytochromeInorganic chemistry · 2019Article
- A Robust Model for Circadian Redox Oscillations.International journal of molecular sciences · 2019Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Rev-erbβ is a heme-binding nuclear hormone receptor that represses a broad spectrum of target genes involved in regulating metabolism, the circadian cycle, and proinflammatory responses. Here, we demonstrate that a thiol-disulfide redox switch controls the interaction between heme and the ligand-binding domain of Rev-erbβ. The reduced dithiol state of Rev-erbβ binds heme 5-fold more tightly than the oxidized disulfide state. By means of site-directed mutagenesis and by UV-visible and EPR spectroscopy, we also show that the ferric heme of reduced (dithiol) Rev-erbβ can undergo a redox-triggered switch from imidazole/thiol ligation (via His-568 and Cys-384, based on a prior crystal structure) to His/neutral residue ligation upon oxidation to the disulfide form. On the other hand, we find that change in the redox state of iron has no effect on heme binding to the ligand-binding domain of the protein. The low dissociation constant for the complex between Fe(3+)- or Fe(2+)-heme and the reduced dithiol state of the protein (K(d) = ∼ 20 nM) is in the range of the intracellular free heme concentration. We also determined that the Fe(2+)-heme bound to the ligand-binding domain of Rev-erbβ has high affinity for CO (K(d) = 60 nM), which replaces one of the internal ligands when bound. We suggest that this thiol-disulfide redox switch is one mechanism by which oxidative stress is linked to circadian and/or metabolic imbalance. Heme dissociation from Rev-erbβ has been shown to derepress the expression of target genes in response to changes in intracellular redox conditions. We propose that oxidative stress leads to oxidation of cysteine(s), thus releasing heme from Rev-erbβ and altering its transcriptional activity.
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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.