Crystal structure of a heterodimeric complex of RAR and RXR ligand-binding domains

Mol Cell. 2000 Feb;5(2):289-98. doi: 10.1016/s1097-2765(00)80424-4.

Abstract

The crystal structure of a heterodimer between the ligand-binding domains (LBDs) of the human RARalpha bound to a selective antagonist and the constitutively active mouse RXRalphaF318A mutant shows that, pushed by a bulky extension of the ligand, RARalpha helix H12 adopts an antagonist position. The unexpected presence of a fatty acid in the ligand-binding pocket of RXRalpha(F318A is likely to account for its apparent "constitutivity." Specific conformational changes suggest the structural basis of pure and partial antagonism. The RAR-RXR heterodimer interface is similar to that observed in most nuclear receptor (NR) homodimers. A correlative analysis of 3D structures and sequences provides a novel view on dimerization among members of the nuclear receptor superfamily.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Benzoates / pharmacology
  • Binding Sites
  • Crystallography, X-Ray
  • Dimerization
  • Fatty Acids / isolation & purification
  • Humans
  • Ligands
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Receptors, Retinoic Acid / antagonists & inhibitors
  • Receptors, Retinoic Acid / chemistry*
  • Receptors, Retinoic Acid / genetics
  • Recombinant Proteins / chemistry
  • Retinoic Acid Receptor alpha
  • Retinoid X Receptors
  • Retinoids / pharmacology
  • Signal Transduction
  • Surface Properties
  • Transcription Factors / chemistry*
  • Transcription Factors / genetics

Substances

  • Benzoates
  • Fatty Acids
  • Ligands
  • RARA protein, human
  • Rara protein, mouse
  • Receptors, Retinoic Acid
  • Recombinant Proteins
  • Retinoic Acid Receptor alpha
  • Retinoid X Receptors
  • Retinoids
  • Transcription Factors
  • SR 11237

Associated data

  • PDB/1DKF