8d8i
From Proteopedia
Crystal structure of Reverb alpha in complex with synthetic agonist
Structural highlights
FunctionNR1D1_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 PubMedThe 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
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