1G1U

THE 2.5 ANGSTROM RESOLUTION CRYSTAL STRUCTURE OF THE RXRALPHA LIGAND BINDING DOMAIN IN TETRAMER IN THE ABSENCE OF LIGAND

Summary for 1G1U

• Entry DOI: 10.2210/pdb1g1u/pdb
• Related: 1FM6 1FM9 1LBD
• Descriptor: RETINOIC ACID RECEPTOR RXR-ALPHA (2 entities in total)
• Functional Keywords: rxralpha ligand binding domain, tetramer, absence of ligand, transcription
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus : P19793
• Total number of polymer chains: 4
• Total formula weight: 106671.43

Authors

Gampe Jr., R.T.,Montana, V.G.,Lambert, M.H.,Wisely, G.B.,Milburn, M.V.,Xu, H.E. (deposition date: 2000-10-13, release date: 2001-04-25, Last modification date: 2024-10-16)

Primary citation

Gampe Jr., R.T.,Montana, V.G.,Lambert, M.H.,Wisely, G.B.,Milburn, M.V.,Xu, H.E.
Structural basis for autorepression of retinoid X receptor by tetramer formation and the AF-2 helix.
Genes Dev., 14:2229-2241, 2000

PubMed Abstract: The 9-cis-retinoic acid receptors (RXRalpha, RXRbeta, and RXRgamma) are nuclear receptors that play key roles in multiple hormone-signaling pathways. Biochemical data indicate that, in the absence of ligand, RXR can exist as an inactive tetramer and that its dissociation, induced by ligand, is important for receptor activation. In this article we report the inactivated tetramer structures of the RXRalpha ligand-binding domain (LBD), either in the absence of or in the presence of a nonactivating ligand. These structures reveal that the RXR LBD tetramer forms a compact, disc-shaped complex, consisting of two symmetric dimers that are packed along helices 3 and 11. In each monomer, the AF-2 helix protrudes away from the core domain and spans into the coactivator binding site in the adjacent monomer of the symmetric dimer. In this configuration, the AF-2 helix physically excludes the binding of coactivators and suggests an autorepression mechanism that is mediated by the AF-2 helix within the tetramer. The RXR-tetramer interface is assembled from amino acids that are conserved across several closely related receptors, including the HNF4s and COUP transcription factors, and may therefore provide a model for understanding structure and regulation of this subfamily of nuclear receptors.

PubMed: 10970886
DOI: 10.1101/gad.802300

Experimental method

X-RAY DIFFRACTION (2.5 Å)