Details

Autor(en) / Beteiligte

• Osz, Judit
• McEwen, Alastair G.
• Wolf, Justine
• Poussin-Courmontagne, Pierre
• Peluso-Iltis, Carole
• Chebaro, Yassmine
• Kieffer, Bruno
• Rochel, Natacha

Titel

Modulation of RXR-DNA complex assembly by DNA context

Ist Teil von

• Molecular and cellular endocrinology, 2019-02, Vol.481, p.44-52

Ort / Verlag

Ireland: Elsevier B.V

Erscheinungsjahr

2019

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. •Crystal structure of RXR homodimer DNA binding domain in complex with MEp DR1.•NMR characterization of RXR homodimer interaction with DNA.•Half-site DR1 sequences modulate the binding cooperativity resulting from protein-protein contacts.•NMR chemical shift perturbations showed the impact of the DNA sequence on the RXR dimer's dynamics.