Crystal structure of the RAR-gamma ligand-binding domain bound to all-trans retinoic acid.
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.
Renaud
J P
JP
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP/Collège de France, Strasbourg, France.
Rochel
N
N
Ruff
M
M
Vivat
V
V
Chambon
P
P
Gronemeyer
H
H
Moras
D
D
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D003196:Computer Graphics; D018360:Crystallography, X-Ray; D004563:Electrochemistry; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017510:Protein Folding; D018168:Receptors, Retinoic Acid / Q000737:chemistry* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015533:Transcriptional Activation; D014212:Tretinoin / Q000737:chemistry* / Q000378:metabolism; D000097768:Retinoic Acid Receptor gamma
D018168:Receptors, Retinoic Acid; D014212:Tretinoin; D000097768:Retinoic Acid Receptor gamma