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http://purl.uniprot.org/citations/28500133http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/28500133http://www.w3.org/2000/01/rdf-schema#comment"Rev-erbβ is a heme-responsive transcription factor that regulates genes involved in circadian rhythm maintenance and metabolism, effectively bridging these critical cellular processes. Heme binding to Rev-erbβ indirectly facilitates its interaction with the nuclear receptor co-repressor (NCoR1), resulting in repression of Rev-erbβ target genes. Fe3+-heme binds in a 6-coordinate complex with axial His and Cys ligands, the latter provided by a heme-regulatory motif (HRM). Rev-erbβ was thought to be a heme sensor based on a weak Kd value for the Rev-erbβ·heme complex of 2 μm determined with isothermal titration calorimetry. However, our group demonstrated with UV-visible difference titrations that the Kd value is in the low nanomolar range, and the Fe3+-heme off-rate is on the order of 10-6 s-1 making Rev-erbβ ineffective as a sensor of Fe3+-heme. In this study, we dissected the kinetics of heme binding to Rev-erbβ and provided a Kd for Fe3+-heme of ∼0.1 nm Loss of the HRM axial thiolate via redox processes, including oxidation to a disulfide with a neighboring cysteine or dissociation upon reduction of Fe3+-to Fe2+-heme, decreased binding affinity by >20-fold. Furthermore, as measured in a co-immunoprecipitation assay, substitution of the His or Cys heme ligands in Rev-erbβ was accompanied by a significant loss of NCoR1 binding. These results demonstrate the importance of the Rev-erbβ HRM in regulating interactions with heme and NCoR1 and advance our understanding of how signaling through HRMs affects the major cellular processes of circadian rhythm maintenance and metabolism."xsd:string
http://purl.uniprot.org/citations/28500133http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m117.783118"xsd:string
http://purl.uniprot.org/citations/28500133http://purl.uniprot.org/core/author"Carter E.L."xsd:string
http://purl.uniprot.org/citations/28500133http://purl.uniprot.org/core/author"Ragsdale S.W."xsd:string
http://purl.uniprot.org/citations/28500133http://purl.uniprot.org/core/author"Ramirez Y."xsd:string
http://purl.uniprot.org/citations/28500133http://purl.uniprot.org/core/date"2017"xsd:gYear
http://purl.uniprot.org/citations/28500133http://purl.uniprot.org/core/name"J Biol Chem"xsd:string
http://purl.uniprot.org/citations/28500133http://purl.uniprot.org/core/pages"11280-11299"xsd:string
http://purl.uniprot.org/citations/28500133http://purl.uniprot.org/core/title"The heme-regulatory motif of nuclear receptor Rev-erbbeta is a key mediator of heme and redox signaling in circadian rhythm maintenance and metabolism."xsd:string
http://purl.uniprot.org/citations/28500133http://purl.uniprot.org/core/volume"292"xsd:string
http://purl.uniprot.org/citations/28500133http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/28500133
http://purl.uniprot.org/citations/28500133http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/28500133
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