7BK4

Crystal structure of RXRalpha ligand binding domain in complex with a fragment of the TIF2 coactivator

Summary for 7BK4

• Entry DOI: 10.2210/pdb7bk4/pdb
• Descriptor: Retinoic acid receptor RXR-alpha, Nuclear receptor coactivator 2, 6-[1-(3,5,5,8,8-PENTAMETHYL-5,6,7,8-TETRAHYDRONAPHTHALEN-2-YL)CYCLOPROPYL]PYRIDINE-3-CARBOXYLIC ACID, ... (4 entities in total)
• Functional Keywords: nuclear receptor, ligand binding domain, coactivator, transcription
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 61395.13

Authors

le Maire, A.,Bourguet, W. (deposition date: 2021-01-15, release date: 2021-08-04, Last modification date: 2024-01-31)

Primary citation

Senicourt, L.,le Maire, A.,Allemand, F.,Carvalho, J.E.,Guee, L.,Germain, P.,Schubert, M.,Bernado, P.,Bourguet, W.,Sibille, N.
Structural Insights into the Interaction of the Intrinsically Disordered Co-activator TIF2 with Retinoic Acid Receptor Heterodimer (RXR/RAR).
J.Mol.Biol., 433:166899-166899, 2021

PubMed 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 (TIF2) 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 by integrating several experimental (NMR, SAXS, Far-UV 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 in complex with RXR/RAR reveal a multisite binding of the three NR-boxes as well as an active role of their flanking regions in the interaction.

PubMed: 33647291
DOI: 10.1016/j.jmb.2021.166899

Experimental method

X-RAY DIFFRACTION (2.8 Å)