Structural highlights
Function
[RXRA_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 PubMed
The retinoid X receptor (RXR) is a member of the nuclear hormone receptor superfamily of transcriptional regulators and plays a central role in the retinoid and, through its ability to heterodimerize with other nuclear hormone receptors, non-steroid signaling pathways. The DNA-binding and recognition functions of RXR are located in a conserved 83 amino acid residue domain that recognizes the consensus sequence AGGTCA. In order to provide a detailed picture of its structure, we have calculated a high-resolution solution structure of the C195A RXRalpha DNA-binding domain. Structures were calculated using 1131 distance and dihedral angle constraints derived from 1H, 13C and 15N NMR spectra. The structures reveal a perpendicularly packed, "loop-helix" fold similar to other nuclear hormone receptor DNA-binding domains and confirm the existence of the C-terminal helix, which was first observed in the low-resolution NMR structure. The C-terminal helix is well formed and is stabilized by packing interactions with residues in the hydrophobic core. The solution structure of RXR is very similar to that determined by X-ray crystallographic studies of the RXR-TR heterodimer complex with DNA, except that in the latter case no electron density was observed for residues corresponding to the C-terminal helix. Other differences between the X-ray and NMR structures occur in the second zinc-binding loop, which is disordered in solution. Heteronuclear 15N NOE measurements suggest that this loop has enhanced flexibility in the free protein.
High-resolution solution structure of the retinoid X receptor DNA-binding domain.,Holmbeck SM, Foster MP, Casimiro DR, Sem DS, Dyson HJ, Wright PE J Mol Biol. 1998 Aug 14;281(2):271-84. PMID:9698548[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Gorla-Bajszczak A, Juge-Aubry C, Pernin A, Burger AG, Meier CA. Conserved amino acids in the ligand-binding and tau(i) domains of the peroxisome proliferator-activated receptor alpha are necessary for heterodimerization with RXR. Mol Cell Endocrinol. 1999 Jan 25;147(1-2):37-47. PMID:10195690
- ↑ Harish S, Ashok MS, Khanam T, Rangarajan PN. Serine 27, a human retinoid X receptor alpha residue, phosphorylated by protein kinase A is essential for cyclicAMP-mediated downregulation of RXRalpha function. Biochem Biophys Res Commun. 2000 Dec 29;279(3):853-7. PMID:11162439 doi:10.1006/bbrc.2000.4043
- ↑ Tsutsumi T, Suzuki T, Shimoike T, Suzuki R, Moriya K, Shintani Y, Fujie H, Matsuura Y, Koike K, Miyamura T. Interaction of hepatitis C virus core protein with retinoid X receptor alpha modulates its transcriptional activity. Hepatology. 2002 Apr;35(4):937-46. PMID:11915042 doi:10.1053/jhep.2002.32470
- ↑ Santos NC, Kim KH. Activity of retinoic acid receptor-alpha is directly regulated at its protein kinase A sites in response to follicle-stimulating hormone signaling. Endocrinology. 2010 May;151(5):2361-72. doi: 10.1210/en.2009-1338. Epub 2010 Mar , 9. PMID:20215566 doi:10.1210/en.2009-1338
- ↑ Holmbeck SM, Foster MP, Casimiro DR, Sem DS, Dyson HJ, Wright PE. High-resolution solution structure of the retinoid X receptor DNA-binding domain. J Mol Biol. 1998 Aug 14;281(2):271-84. PMID:9698548 doi:http://dx.doi.org/10.1006/jmbi.1998.1908
