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Nat Struct Biol. 1996 Jan;3(1):87-94.

A canonical structure for the ligand-binding domain of nuclear receptors.

Author information

1
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP/C, Collège de France, Illkrich, C.U. de Strasbourg, France.

Abstract

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.

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PMID:
8548460
DOI:
10.1038/nsb0196-87
[Indexed for MEDLINE]

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