Crystal structure of the RAR-gamma ligand-binding domain bound to all-trans retinoic acid

Nature. 1995 Dec 14;378(6558):681-9. doi: 10.1038/378681a0.


The 2.0-A crystal structure of the ligand-binding domain (LBD) of the human retinoic acid receptor (RAR)-gamma bound to all-trans retinoic acid reveals the ligand-binding interactions and suggests an electrostatic guidance mechanism. The overall fold is similar to that of the human RXR-alpha apo-LBD, except for the carboxy-terminal part which folds back towards the LBD core, contributing to the hydrophobic ligand pocket and 'sealing' its entry site. We propose a 'mouse trap' mechanism whereby a ligand-induced conformational transition repositions the amphipathic alpha-helix of the AF-2 activating domain and forms a transcriptionally active receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Computer Graphics
  • Crystallography, X-Ray
  • Electrochemistry
  • Humans
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Conformation
  • Protein Folding
  • Receptors, Retinoic Acid / chemistry*
  • Receptors, Retinoic Acid / metabolism
  • Sequence Homology, Amino Acid
  • Transcriptional Activation
  • Tretinoin / chemistry*
  • Tretinoin / metabolism


  • Receptors, Retinoic Acid
  • retinoic acid receptor gamma
  • Tretinoin