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STRUCTURE AND MECHANISM OF THE HOMODIMERIC ASSEMBLY OF THE RXR ON DNA
Structural highlights
FunctionRXRA_HUMAN Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. The high affinity ligand for RXRs is 9-cis retinoic acid. RXRA serves as a common heterodimeric partner for a number of nuclear receptors. The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone acetylation, chromatin condensation and transcriptional suppression. On ligand binding, the corepressors dissociate from the receptors and associate with the coactivators leading to transcriptional activation. The RXRA/PPARA heterodimer is required for PPARA transcriptional activity on fatty acid oxidation genes such as ACOX1 and the P450 system genes.[1] [2] [3] [4] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe 9-cis retinoic acid receptor, RXR, binds DNA effectively as a homodimer or as a heterodimer with other nuclear receptors. The DNA-binding sites for these RXR complexes are direct repeats of a consensus sequence separated by one to five base-pairs of intervening space. Here, we report the 2.1 A crystal structure of the RXR-DNA-binding domain as a homodimer in complex with its idealized direct repeat DNA target. The structure shows how a gene-regulatory site can induce conformational changes in a transcription factor that promote homo-cooperative assembly. Specifically, an alpha-helix in the T-box is disrupted to allow efficient DNA-binding and subunit dimerization. RXR displays a relaxed mode of sequence recognition, interacting with only three base-pairs in each hexameric half-site. The structure illustrates how site selection is achieved in this large eukaryotic transcription factor family through discrete protein-protein interactions and the use of tandem DNA binding sites with characteristic spacings. Structural basis of RXR-DNA interactions.,Zhao Q, Chasse SA, Devarakonda S, Sierk ML, Ahvazi B, Rastinejad F J Mol Biol. 2000 Feb 18;296(2):509-20. PMID:10669605[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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