5UAN

Crystal structure of multi-domain RAR-beta-RXR-alpha heterodimer on DNA

Summary for 5UAN

• Entry DOI: 10.2210/pdb5uan/pdb
• Descriptor: Retinoic acid receptor RXR-alpha, Retinoic acid receptor beta, Nuclear receptor coactivator 2, ... (8 entities in total)
• Functional Keywords: nuclear receptors, transcription, protein-dna complex, transcription-dna complex, transcription/dna
• Biological source: Homo sapiens (Human); More
• Cellular location: Nucleus : P19793 E7EWM1; Isoform Beta-1: Nucleus. Isoform Beta-2: Nucleus. Isoform Beta-4: Cytoplasm: P10826
• Total number of polymer chains: 6
• Total formula weight: 99768.27

Authors

Chandra, V.,Wu, D.,Kim, Y.,Rastinejad, F. (deposition date: 2016-12-19, release date: 2017-10-18, Last modification date: 2023-10-04)

Primary citation

Chandra, V.,Wu, D.,Li, S.,Potluri, N.,Kim, Y.,Rastinejad, F.
The quaternary architecture of RAR beta-RXR alpha heterodimer facilitates domain-domain signal transmission.
Nat Commun, 8:868-868, 2017

PubMed Abstract: Assessing the physical connections and allosteric communications in multi-domain nuclear receptor (NR) polypeptides has remained challenging, with few crystal structures available to show their overall structural organizations. Here we report the quaternary architecture of multi-domain retinoic acid receptor β-retinoic X receptor α (RARβ-RXRα) heterodimer bound to DNA, ligands and coactivator peptides, examined through crystallographic, hydrogen-deuterium exchange mass spectrometry, mutagenesis and functional studies. The RARβ ligand-binding domain (LBD) and DNA-binding domain (DBD) are physically connected to foster allosteric signal transmission between them. Direct comparisons among all the multi-domain NRs studied crystallographically to date show significant variations within their quaternary architectures, rather than a common architecture adhering to strict rules. RXR remains flexible and adaptive by maintaining loosely organized domains, while its heterodimerization partners use a surface patch on their LBDs to form domain-domain interactions with DBDs.Nuclear receptors (NR) are multidomain proteins, which makes their crystallization challenging. Here the authors present the crystal structure of the retinoic acid receptor β-retinoic X receptor α (RARβ-RXRα) heterodimer bound to DNA, ligands and coactivator peptides, which shows that NR quaternary architectures are variable.

PubMed: 29021580
DOI: 10.1038/s41467-017-00981-y

Experimental method

X-RAY DIFFRACTION (3.508 Å)