Structural highlights
Function
NR1D1_HUMAN Functions as a constitutive transcriptional repressor. In collaboration with SP1, activates GJA1 transcription (By similarity). Possible receptor for triiodothyronine.[1] [2]
Publication Abstract from PubMed
The nuclear receptor REV-ERB plays an important role in a range of physiological processes. REV-ERB behaves as a ligand-dependent transcriptional repressor and heme has been identified as a physiological agonist. Our current understanding of how ligands bind to and regulate transcriptional repression by REV-ERB is based on the structure of heme bound to REV-ERB. However, porphyrin (heme) analogues have been avoided as a source of synthetic agonists due to the wide range of heme binding proteins and potential pleotropic effects. How non-porphyrin synthetic agonists bind to and regulate REV-ERB has not yet been defined. Here, we characterize a high affinity synthetic REV-ERB agonist, STL1267, and describe its mechanism of binding to REV-ERB as well as the method by which it recruits transcriptional corepressor both of which are unique and distinct from that of heme-bound REV-ERB.
Structural basis of synthetic agonist activation of the nuclear receptor REV-ERB.,Murray MH, Valfort AC, Koelblen T, Ronin C, Ciesielski F, Chatterjee A, Veerakanellore GB, Elgendy B, Walker JK, Hegazy L, Burris TP Nat Commun. 2022 Nov 21;13(1):7131. doi: 10.1038/s41467-022-34892-4. PMID:36414641[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Miyajima N, Horiuchi R, Shibuya Y, Fukushige S, Matsubara K, Toyoshima K, Yamamoto T. Two erbA homologs encoding proteins with different T3 binding capacities are transcribed from opposite DNA strands of the same genetic locus. Cell. 1989 Apr 7;57(1):31-9. PMID:2539258
- ↑ Lazar MA, Jones KE, Chin WW. Isolation of a cDNA encoding human Rev-ErbA alpha: transcription from the noncoding DNA strand of a thyroid hormone receptor gene results in a related protein that does not bind thyroid hormone. DNA Cell Biol. 1990 Mar;9(2):77-83. PMID:1971514
- ↑ Murray MH, Valfort AC, Koelblen T, Ronin C, Ciesielski F, Chatterjee A, Veerakanellore GB, Elgendy B, Walker JK, Hegazy L, Burris TP. Structural basis of synthetic agonist activation of the nuclear receptor REV-ERB. Nat Commun. 2022 Nov 21;13(1):7131. doi: 10.1038/s41467-022-34892-4. PMID:36414641 doi:http://dx.doi.org/10.1038/s41467-022-34892-4
