6fbq

From Proteopedia

(Difference between revisions)

Current revision

Crystal Structure of the Human Retinoid X Receptor DNA-Binding Domain Bound to the Human MEp DR1 Response Element, pH 7.0

Structural highlights

6fbq is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Gene:	RXRA, NR2B1 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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]

Publication Abstract from PubMed

Retinoid X Receptors (RXRs) act as dimer partners for several nuclear receptors including itself, binding to genomic DNA response elements and regulating gene transcription with cell and gene specificity. As homodimers, RXRs bind direct repeats of the half-site (A/G)G(G/T)TCA separated by 1 nucleotide (DR1) and little variability of this consensus site is observed for natural DR1s. However, these variations are responsible of the modulation of RXR receptors function through differential binding affinity and conformational changes. To further our understanding of the molecular mechanisms underlying RXR-DNA interactions, we examined how RXR DBDs bind to different DR1s using thermodynamics, X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy. We show that the half-site sequences modulate the binding cooperativity that results from the protein-protein contacts between the two DBDs. Chemical shifts perturbation NMR experiments revealed that sequence variations in half-sites induce changes that propagate from the protein-DNA interface to the dimerization interface throughout the DBD fold.

Modulation of RXR-DNA complex assembly by DNA context.,Osz J, McEwen AG, Wolf J, Poussin-Courmontagne P, Peluso-Iltis C, Chebaro Y, Kieffer B, Rochel N Mol Cell Endocrinol. 2018 Nov 23. pii: S0303-7207(18)30340-X. doi:, 10.1016/j.mce.2018.11.008. PMID:30476562^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ Osz J, McEwen AG, Wolf J, Poussin-Courmontagne P, Peluso-Iltis C, Chebaro Y, Kieffer B, Rochel N. Modulation of RXR-DNA complex assembly by DNA context. Mol Cell Endocrinol. 2018 Nov 23. pii: S0303-7207(18)30340-X. doi:, 10.1016/j.mce.2018.11.008. PMID:30476562 doi:http://dx.doi.org/10.1016/j.mce.2018.11.008

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6fbq"

@@ Line 3: / Line 3: @@
 <StructureSection load='6fbq' size='340' side='right' caption='[[6fbq]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6fbq]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FBQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FBQ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6fbq]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FBQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FBQ FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MPO:3[N-MORPHOLINO]PROPANE+SULFONIC+ACID'>MPO</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RXRA, NR2B1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6fbq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fbq OCA], [http://pdbe.org/6fbq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fbq RCSB], [http://www.ebi.ac.uk/pdbsum/6fbq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fbq ProSAT]</span></td></tr>
 </table>
@@ Line 22: / Line 23: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: McEwen, A G]]
 [[Category: Osz, J]]

6fbq

From Proteopedia

Current revision

Crystal Structure of the Human Retinoid X Receptor DNA-Binding Domain Bound to the Human MEp DR1 Response Element, pH 7.0

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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