Structural Insights into the Interaction of the Intrinsically Disordered Co-activator TIF2 with Retinoic Acid Receptor Heterodimer (RXR/RAR)

Retinoic acid receptors (RARs) and retinoid X (RXRs) form heterodimers that activate target gene transcription by recruiting co-activator complexes in response to ligand binding. The nuclear receptor (NR) TIF2 mediates this recruitment interacting with the ligand-binding domain (LBD) of NRs trough interaction (TIF2NRID) containing three highly conserved ?-helical LxxLL motifs (NR-boxes). precise binding mode RXR/RAR is not clear due disordered nature TIF2. Here we present structural characterization TIF2NRID integrating several experimental (NMR, SAXS, Far-UV CD, SEC-MALS) computational data. Collectively, data are agreement a largely protein partially structured regions, including NR-boxes their flanking which evolutionary conserved. NMR X-ray crystallographic on complex reveal multisite as well an active role regions interaction.