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The quaternary architecture of RARβ–RXRα heterodimer facilitates domain–domain signal transmission

Author

Listed:
  • Vikas Chandra

    (Integrative Metabolism Program, Sanford Burnham Prebys Medical Discovery Institute)

  • Dalei Wu

    (Integrative Metabolism Program, Sanford Burnham Prebys Medical Discovery Institute
    Shandong University-Helmholtz Institute of Biotechnology, State Key Laboratory of Microbial Technology, School of Life Sciences, Shandong University)

  • Sheng Li

    (University of California, San Diego)

  • Nalini Potluri

    (Integrative Metabolism Program, Sanford Burnham Prebys Medical Discovery Institute)

  • Youngchang Kim

    (Structural Biology Center, Biosciences Division, Argonne National Laboratory)

  • Fraydoon Rastinejad

    (Integrative Metabolism Program, Sanford Burnham Prebys Medical Discovery Institute)

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.

Suggested Citation

  • Vikas Chandra & Dalei Wu & Sheng Li & Nalini Potluri & Youngchang Kim & Fraydoon Rastinejad, 2017. "The quaternary architecture of RARβ–RXRα heterodimer facilitates domain–domain signal transmission," Nature Communications, Nature, vol. 8(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00981-y
    DOI: 10.1038/s41467-017-00981-y
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    Cited by:

    1. Devesh Bhimsaria & José A. Rodríguez-Martínez & Jacqui L. Mendez-Johnson & Debostuti Ghoshdastidar & Ashwin Varadarajan & Manju Bansal & Danette L. Daniels & Parameswaran Ramanathan & Aseem Z. Ansari, 2023. "Hidden modes of DNA binding by human nuclear receptors," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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