Molecular determinants of MED1 interaction with the DNA bound VDR–RXR heterodimer - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Nucleic Acids Research Année : 2020

Molecular determinants of MED1 interaction with the DNA bound VDR–RXR heterodimer

Résumé

The MED1 subunit of the Mediator complex is an essential coactivator of nuclear receptor-mediated transcriptional activation. While structural requirements for ligand-dependent binding of classical coactivator motifs of MED1 to numerous nuclear receptor ligand-binding domains have been fully elucidated, the recognition of the full-length or truncated coactivator by full nuclear receptor complexes remain unknown. Here we present structural details of the interaction between a large part of MED1 comprising its structured N-terminal and the flexible receptor-interacting domains and the mutual heterodimer of the vitamin D receptor (VDR) and the retinoid X receptor (RXR) bound to their cognate DNA response element. Using a combination of structural and biophysical methods we show that the ligand-dependent interaction between VDR and the second coactivator motif of MED1 is crucial for complex formation and we identify additional, previously unseen, interaction details. In particular, we identified RXR regions involved in the interaction with the structured N-terminal domain of MED1, as well as VDR regions outside the classical coactivator binding cleft affected by coactivator recruitment. These findings highlight important roles of each receptor within the heterodimer in selective recognition of MED1 and contribute to our understanding of the nuclear receptor-coregulator complexes.
Fichier principal
Vignette du fichier
Rochel Med1 NAR2020.PDF (1.49 Mo) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)
Loading...

Dates et versions

hal-02962412 , version 1 (09-10-2020)

Identifiants

Citer

Y Belorusova Anna, Maxime Bourguet, Steve Hessmann, Sandra Chalhoub, Bruno Kieffer, et al.. Molecular determinants of MED1 interaction with the DNA bound VDR–RXR heterodimer. Nucleic Acids Research, 2020, ⟨10.1093/nar/gkaa775⟩. ⟨hal-02962412⟩
121 Consultations
101 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More