Modulation of RXR-DNA complex assembly by DNA context.
Fiche publication
Date publication
novembre 2018
Journal
Molecular and cellular endocrinology
Auteurs
Membres identifiés du Cancéropôle Est :
Dr KIEFFER Bruno, Dr ROCHEL-GUIBERTEAU Natacha, Dr OSZ-PAPAI Judit
Tous les auteurs :
Osz J, McEwen AG, Wolf J, Poussin-Courmontagne P, Peluso-Iltis C, Chebaro Y, Kieffer B, Rochel N
Lien Pubmed
Résumé
Retinoid X Receptors (RXRs) act as dimer partners for several nuclear receptors including itself, binding to genomic DNA response elements and regulating gene transcription with cell and gene specificity. As homodimers, RXRs bind direct repeats of the half-site (A/G)G(G/T)TCA separated by 1 nucleotide (DR1) and little variability of this consensus site is observed for natural DR1s. However, these variations are responsible of the modulation of RXR receptors function through differential binding affinity and conformational changes. To further our understanding of the molecular mechanisms underlying RXR-DNA interactions, we examined how RXR DBDs bind to different DR1s using thermodynamics, X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy. We show that the half-site sequences modulate the binding cooperativity that results from the protein-protein contacts between the two DBDs. Chemical shifts perturbation NMR experiments revealed that sequence variations in half-sites induce changes that propagate from the protein-DNA interface to the dimerization interface throughout the DBD fold.
Mots clés
DNA, Homodimer, NMR, Nuclear receptor, RXR, X-ray crystallography
Référence
Mol. Cell. Endocrinol.. 2018 Nov 23;: