Structural basis of synthetic agonist activation of the nuclear receptor REV-ERB.
Nat Commun
; 13(1): 7131, 2022 11 21.
Article
em En
| MEDLINE
| ID: mdl-36414641
ABSTRACT
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.
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1
Base de dados:
MEDLINE
Assunto principal:
Porfirinas
/
Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article