Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.28.359091v1?rss=1 Authors: Senicourt, L., le Maire, A., Allemand, F., Carvalho, J. E., Guee, L., Germain, P., Schubert, M., Bernado, P., Bourguet, W., Sibille, N. Abstract: 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 (TIF2NRID) containing three highly conserved -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 TIF2NRID 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 TIF2NRID 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. Copy rights belong to original authors. Visit the link for more info