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

Nature Structural Biology volume 3, pages 87–94 (1996)Cite this article

An Erratum to this article was published on 01 February 1996

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 RXRα and the liganded RARγ LBDs has been incorporated into a general alignment of the LBDs of all NRs. A twenty amino-acid region constitutes a NR-specif ic 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 RXRα and glucocorticoid receptor ligand-binding sites according to the RARγ 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 RARγ holo- and inactive RXRα apo-LBD structures.

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  1. Institut de Génétique et de Biologie Moléculaireet Cellulaire, CNRS/INSERM/ULP/C Collège de France, BP 163, F-67404, Illkirch Cédex, CU.de Strasbourg, France

    Jean-Marie Wurtz, William Bourguet, Jean-Paul Renaud, Valérie Vivat, Pierre Chambon, Dino Moras & Hinrich Gronemeyer

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Wurtz, JM., Bourguet, W., Renaud, JP. et al. A canonical structure for the ligand-binding domain of nuclear receptors. Nat Struct Mol Biol 3, 87–94 (1996). https://doi.org/10.1038/nsb0196-87

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