Structural insights into the cooperative interaction of the intrinsically disordered co-activator TIF2 with retinoic acid receptor heterodimer (RXR/RAR) - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Pré-Publication, Document De Travail Année : 2020

Structural insights into the cooperative interaction of the intrinsically disordered co-activator TIF2 with retinoic acid receptor heterodimer (RXR/RAR)

Lucile Senicourt
  • Fonction : Auteur
Albane Le Maire
  • Fonction : Auteur
Frédéric Allemand
João Carvalho
  • Fonction : Auteur
Laura Guee
  • Fonction : Auteur
Pierre Germain
  • Fonction : Auteur
Michael Schubert
Pau Bernadó
William Bourguet

Résumé

Retinoic acid receptors (RARs) and retinoid X receptors (RXRs) form heterodimers that activate target gene transcription by recruiting co-activator complexes in response to ligand binding. The nuclear receptor (NR) co-activator TIF2 mediates this recruitment by interacting with the ligand-binding domain (LBD) of NRs trough the nuclear receptor interaction domain (TIF2 NRID ) containing three highly conserved α-helical LxxLL motifs (NR-boxes). The precise binding mode of this domain to RXR/RAR is not clear due to the disordered nature of TIF2. Here we present the structural characterization of TIF2 NRID by integrating several experimental (NMR, SAXS, CD, SEC-MALS) and computational data. Collectively, the data are in agreement with a largely disordered protein with partially structured regions, including the NR-boxes and their flanking regions, which are evolutionary conserved. NMR and X-ray crystallographic data on TIF2 NRID in complex with RXR/RAR reveal a cooperative binding of the three NR-boxes as well as an active role of their flanking regions in the interaction.
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Dates et versions

hal-03047222 , version 1 (16-12-2020)
hal-03047222 , version 2 (09-11-2021)

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Lucile Senicourt, Albane Le Maire, Frédéric Allemand, João Carvalho, Laura Guee, et al.. Structural insights into the cooperative interaction of the intrinsically disordered co-activator TIF2 with retinoic acid receptor heterodimer (RXR/RAR). 2020. ⟨hal-03047222v1⟩
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