Structural basis of the farnesoid X receptor/retinoid X receptor heterodimer on inverted repeat DNA.
Crystal structure
Farnesoid X receptor
Heterodimer
Inverted repeat DNA
Retinoid X receptor
Journal
Computational and structural biotechnology journal
ISSN: 2001-0370
Titre abrégé: Comput Struct Biotechnol J
Pays: Netherlands
ID NLM: 101585369
Informations de publication
Date de publication:
2023
2023
Historique:
received:
30
03
2023
revised:
22
05
2023
accepted:
23
05
2023
medline:
8
6
2023
pubmed:
8
6
2023
entrez:
8
6
2023
Statut:
epublish
Résumé
Farnesoid X receptor (FXR) is a ligand-activated transcription factor known as bile acid receptor (BAR). FXR plays critical roles in various biological processes, including metabolism, immune inflammation, liver regeneration and liver carcinogenesis. FXR forms a heterodimer with the retinoid X receptor (RXR) and binds to diverse FXR response elements (FXREs) to exert its various biological functions. However, the mechanism by which the FXR/RXR heterodimer binds the DNA elements remains unclear. In this study, we aimed to use structural, biochemical and bioinformatics analyses to study the mechanism of FXR binding to the typical FXRE, such as the IR1 site, and the heterodimer interactions in the FXR-DBD/RXR-DBD complex. Further biochemical assays showed that RAR, THR and NR4A2 do not form heterodimers with RXR when bound to the IR1 sites, which indicates that IR1 may be a unique binding site for the FXR/RXR heterodimer. Our studies may provide a further understanding of the dimerization specificity of nuclear receptors.
Identifiants
pubmed: 37287811
doi: 10.1016/j.csbj.2023.05.026
pii: S2001-0370(23)00208-8
pmc: PMC10242635
doi:
Types de publication
Journal Article
Langues
eng
Pagination
3149-3157Informations de copyright
© 2023 The Authors.
Déclaration de conflit d'intérêts
The authors declare no competing interests.
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