A canonical structure for the ligand-binding domain of nuclear receptors.
The ability of nuclear receptors (NRs) to activate transcription of target genes requires the binding of cognate ligands to their ligand-binding domains (LBDs). Information provided by the three-dimensional structures of the unliganded RXR alpha and the liganded RAR gamma LBDs has been incorporated into a general alignment of the LBDs of all NRs. A twenty amino-acid region constitutes a NR-specific signature and contains most of the conserved residues that stabilize the core of the canonical fold of NR LBDs. A common ligand-binding pocket, involving predominantly hydrophobic residues, is inferred by homology modelling of the human RXR alpha and glucocorticoid receptor ligand-binding sites according to the RAR gamma holo-LBD structure. Mutant studies support these models, as well as a general mechanism for ligand-induced activation deduced from the comparison of the transcriptionally active RAR gamma holo- and inactive RXR alpha apo-LBD structures.
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP/C, Collège de France, Illkrich, C.U. de Strasbourg, France.
J M
JM
Wurtz
W
W
Bourguet
J P
JP
Renaud
V
V
Vivat
P
P
Chambon
D
D
Moras
H
H
Gronemeyer
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D006801:Humans; D008024:Ligands; D008969:Molecular Sequence Data; D009154:Mutation; D017510:Protein Folding; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment
D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear