Accéder directement au contenu Accéder directement à la navigation
Article dans une revue

Interplay of Protein Disorder in Retinoic Acid Receptor Heterodimer and Its Corepressor Regulates Gene Expression

Abstract : In its unliganded form, the retinoic acid receptor (RAR) in heterodimer with the retinoid X receptor (RXR) exerts a strong repressive activity facilitated by the recruitment of transcriptional corepressors in the promoter region of target genes. By integrating complementary structural, biophysical, and computational information, we demonstrate that intrinsic disorder is a required feature for the precise regulation of RAR activity. We show that structural dynamics of RAR and RXR H12 regions is an essential mechanism for RAR regulation. Unexpectedly we found that, while mainly disordered, the corepressor N-CoR presents evolutionary conserved structured regions involved in transient intramolecular contacts. In the presence of RXR/RAR, N-CoR exploits its multivalency to form a cooperative multisite complex that displays equilibrium between different conformational states that can be tuned by cognate ligands and receptor mutations. This equilibrium is key to preserving the repressive basal state while allowing the conversion to a transcriptionally active form.
Type de document :
Article dans une revue
Liste complète des métadonnées

https://hal.univ-grenoble-alpes.fr/hal-02268989
Contributeur : Frank Thomas <>
Soumis le : jeudi 22 août 2019 - 09:18:34
Dernière modification le : mercredi 15 juillet 2020 - 13:02:04

Lien texte intégral

Identifiants

Citation

Tiago Cordeiro, Nathalie Sibille, Pierre Germain, Philippe Barthe, Abdelhay Boulahtouf, et al.. Interplay of Protein Disorder in Retinoic Acid Receptor Heterodimer and Its Corepressor Regulates Gene Expression. Structure, Elsevier (Cell Press), 2019, 27 (8), pp.1270-1285.e6. ⟨10.1016/j.str.2019.05.001⟩. ⟨hal-02268989⟩

Partager

Métriques

Consultations de la notice

331