Structure of the retinoid X receptor α-liver X receptor β (RXRα-LXRβ) heterodimer on DNA

Nat Struct Mol Biol. 2014 Mar;21(3):277-81. doi: 10.1038/nsmb.2778. Epub 2014 Feb 23.

Abstract

Nuclear receptors (NRs) are conditional transcription factors with common multidomain organization that bind diverse DNA elements. How DNA sequences influence NR conformation is poorly understood. Here we report the crystal structure of the human retinoid X receptor α-liver X receptor β (RXRα-LXRβ) heterodimer on its cognate element, an AGGTCA direct repeat spaced by 4 nt. The complex has an extended X-shaped arrangement, with DNA- and ligand-binding domains crossed, in contrast to the parallel domain arrangement of other NRs that bind an AGGTCA direct repeat spaced by 1 nt. The LXRβ core binds DNA via canonical contacts and auxiliary DNA contacts that enhance affinity for the response element. Comparisons of RXRα-LXRβs in the crystal asymmetric unit and with previous NR structures reveal flexibility in NR organization and suggest a role for RXRα in adaptation of heterodimeric complexes to DNA.

Publication types

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

MeSH terms

  • DNA / chemistry*
  • DNA, Complementary / metabolism
  • Escherichia coli / metabolism
  • Humans
  • Ligands
  • Liver X Receptors
  • Models, Molecular
  • Mutation
  • Orphan Nuclear Receptors / chemistry*
  • Orphan Nuclear Receptors / genetics*
  • Promoter Regions, Genetic
  • Protein Binding
  • Protein Multimerization
  • Protein Structure, Tertiary
  • Retinoid X Receptor alpha / chemistry*
  • Retinoid X Receptor alpha / genetics*
  • Zinc Fingers

Substances

  • DNA, Complementary
  • Ligands
  • Liver X Receptors
  • Orphan Nuclear Receptors
  • Retinoid X Receptor alpha
  • DNA

Associated data

  • PDB/4NQA