Structural basis of synthetic agonist activation of the nuclear receptor REV-ERB.
Nat Commun
; 13(1): 7131, 2022 11 21.
Article
in 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Porphyrins
/
Nuclear Receptor Subfamily 1, Group D, Member 1
Language:
En
Journal:
Nat Commun
Journal subject:
BIOLOGIA
/
CIENCIA
Year:
2022
Type:
Article
Affiliation country:
United States