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

Nat Struct Mol Biol. 2011 May;18(5):556-63. doi: 10.1038/nsmb.2046. Epub 2011 Apr 10.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alitretinoin
  • Binding Sites
  • Dihydroxycholecalciferols / chemistry
  • Humans
  • Ligands
  • Models, Molecular
  • Nuclear Receptor Coactivator 1 / chemistry
  • Promoter Regions, Genetic
  • Protein Interaction Domains and Motifs*
  • Protein Interaction Mapping
  • Protein Stability
  • Protein Structure, Tertiary
  • Receptors, Calcitriol / agonists
  • Receptors, Calcitriol / chemistry*
  • Receptors, Calcitriol / metabolism
  • Retinoid X Receptors / agonists
  • Retinoid X Receptors / chemistry*
  • Retinoid X Receptors / metabolism
  • Tretinoin / chemistry


  • Dihydroxycholecalciferols
  • Ligands
  • Receptors, Calcitriol
  • Retinoid X Receptors
  • Alitretinoin
  • Tretinoin
  • NCOA1 protein, human
  • Nuclear Receptor Coactivator 1