Structural basis of RXR-DNA interactions

J Mol Biol. 2000 Feb 18;296(2):509-20. doi: 10.1006/jmbi.1999.3457.


The 9-cis retinoic acid receptor, RXR, binds DNA effectively as a homodimer or as a heterodimer with other nuclear receptors. The DNA-binding sites for these RXR complexes are direct repeats of a consensus sequence separated by one to five base-pairs of intervening space. Here, we report the 2.1 A crystal structure of the RXR-DNA-binding domain as a homodimer in complex with its idealized direct repeat DNA target. The structure shows how a gene-regulatory site can induce conformational changes in a transcription factor that promote homo-cooperative assembly. Specifically, an alpha-helix in the T-box is disrupted to allow efficient DNA-binding and subunit dimerization. RXR displays a relaxed mode of sequence recognition, interacting with only three base-pairs in each hexameric half-site. The structure illustrates how site selection is achieved in this large eukaryotic transcription factor family through discrete protein-protein interactions and the use of tandem DNA binding sites with characteristic spacings.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Allosteric Regulation
  • Amino Acid Sequence
  • Base Pairing / genetics
  • Base Sequence
  • Binding Sites
  • Consensus Sequence / genetics
  • Crystallization
  • Crystallography, X-Ray
  • DNA / chemistry*
  • DNA / genetics
  • DNA / metabolism*
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / metabolism*
  • Dimerization
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Conformation
  • Receptors, Cytoplasmic and Nuclear / chemistry
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Receptors, Retinoic Acid / chemistry*
  • Receptors, Retinoic Acid / metabolism*
  • Repetitive Sequences, Nucleic Acid / genetics
  • Response Elements / genetics
  • Retinoid X Receptors
  • Substrate Specificity
  • Transcription Factors / chemistry*
  • Transcription Factors / metabolism*


  • DNA-Binding Proteins
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Retinoic Acid
  • Retinoid X Receptors
  • Transcription Factors
  • DNA

Associated data

  • PDB/1BY4