DNA binding alters coactivator interaction surfaces of the intact VDR-RXR complex

Jun Zhang, Michael J. Chalmers, Keith R. Stayrook, Lorri L. Burris, Yongjun Wang, Scott A. Busby, Bruce D. Pascal, Ruben D. Garcia-Ordonez, John B. Bruning, Monica A. Istrate, Douglas J. Kojetin, Jeffrey A. Dodge, Thomas P. Burris, Patrick R. Griffin

Research output: Contribution to journalArticle

135 Scopus citations

Abstract

The vitamin D receptor (VDR) functions as an obligate heterodimer in complex with the retinoid X receptor (RXR). These nuclear receptors are multidomain proteins, and it is unclear how various domains interact with one another within the nuclear receptor heterodimer. Here, we show that binding of intact heterodimer to DNA alters the receptor dynamics in regions remote from the DNA-binding domains (DBDs), including the coactivator binding surfaces of both co-receptors, and that the sequence of the DNA response element can determine these dynamics. Furthermore, agonist binding to the heterodimer results in changes in the stability of the VDR DBD, indicating that the ligand itself may play a role in DNA recognition. These data suggest a mechanism by which nuclear receptors show promoter specificity and have differential effects on various target genes, providing insight into the function of selective nuclear receptor modulators.

Original languageEnglish (US)
Pages (from-to)556-563
Number of pages8
JournalNature Structural and Molecular Biology
Volume18
Issue number5
DOIs
StatePublished - May 2011

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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    Zhang, J., Chalmers, M. J., Stayrook, K. R., Burris, L. L., Wang, Y., Busby, S. A., Pascal, B. D., Garcia-Ordonez, R. D., Bruning, J. B., Istrate, M. A., Kojetin, D. J., Dodge, J. A., Burris, T. P., & Griffin, P. R. (2011). DNA binding alters coactivator interaction surfaces of the intact VDR-RXR complex. Nature Structural and Molecular Biology, 18(5), 556-563. https://doi.org/10.1038/nsmb.2046