3r2a: Difference between revisions

From Proteopedia
Jump to navigation Jump to search
← Older edit
No edit summary
No edit summary
 
(One intermediate revision by the same user not shown)
Line 1: Line 1:


==Crystal structure of RXRalpha ligand-binding domain complexed with corepressor SMRT2 and antagonist rhein==
==Crystal structure of RXRalpha ligand-binding domain complexed with corepressor SMRT2 and antagonist rhein==
<StructureSection load='3r2a' size='340' side='right' caption='[[3r2a]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
<StructureSection load='3r2a' size='340' side='right'caption='[[3r2a]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3r2a]] is a 6 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=3R2A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3R2A FirstGlance]. <br>
<table><tr><td colspan='2'>[[3r2a]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3R2A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3R2A FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=RHN:4,5-DIHYDROXY-9,10-DIOXO-9,10-DIHYDROANTHRACENE-2-CARBOXYLIC+ACID'>RHN</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3r29|3r29]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=RHN:4,5-DIHYDROXY-9,10-DIOXO-9,10-DIHYDROANTHRACENE-2-CARBOXYLIC+ACID'>RHN</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'>[https://proteopedia.org/fgij/fg.htm?mol=3r2a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3r2a OCA], [https://pdbe.org/3r2a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3r2a RCSB], [https://www.ebi.ac.uk/pdbsum/3r2a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3r2a ProSAT]</span></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=3r2a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3r2a OCA], [http://pdbe.org/3r2a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3r2a RCSB], [http://www.ebi.ac.uk/pdbsum/3r2a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3r2a ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/RXRA_HUMAN 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.<ref>PMID:10195690</ref> <ref>PMID:11162439</ref> <ref>PMID:11915042</ref> <ref>PMID:20215566</ref>  [[http://www.uniprot.org/uniprot/NCOR2_HUMAN NCOR2_HUMAN]] Transcriptional corepressor of NR4A2/NURR1 and acts through histone deacetylases (HDACs) to keep promoters of NR4A2/NURR1 target genes in a repressed deacetylated state (By similarity). Mediates the transcriptional repression activity of some nuclear receptors by promoting chromatin condensation, thus preventing access of the basal transcription. Isoform 1 and isoform 5 have different affinities for different nuclear receptors.
[https://www.uniprot.org/uniprot/RXRA_HUMAN 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.<ref>PMID:10195690</ref> <ref>PMID:11162439</ref> <ref>PMID:11915042</ref> <ref>PMID:20215566</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Retinoic X receptor (RXR) is a master nuclear receptor in the processes of cell development and homeostasis. Unliganded RXR exists in an auto-repressed tetramer, and agonists can induce RXR dimerization and coactivator recruitment for activation. However, the molecular mechanisms involving the corepressor recruitment and antagonist-mediated repression of RXR are still elusive. Here we reported the crystal structure of RXRalpha ligand-binding domain (LBD) complexed with silencing mediator for retinoid and thyroid hormone receptors (SMRT) corepressor motif. As the first structural report on the unliganded nuclear receptor bound to the corepressor motif, RXRalphaLBD-SMRT exhibited a significant structural rearrangement, compared with the apo RXRalphaLBD tetramer. To further elucidate the molecular determinant for RXR repression by antagonist, we also determined the crystal structure of RXRalphaLBD-SMRT complexed with the identified antagonist rhein. In the structure, two rhein molecules and two SMRT peptides were in the RXRalphaLBD tetramer, different from the case in RXRalphaLBD-SMRT structure, where four SMRT peptides bound to RXR tetramer. It seemed that rhein binding has resulted in a displacement of SMRT motif for activation function-2 (AF-2) motif binding to the receptor. Combining our current work with the published results, structural superposition of RXRalphaLBDs in different states revealed that RXR used an overlapped binding site for coactivator, corepressor and AF-2 motif, while AF-2 motif adopted different conformations for agonist or antagonist interaction, and coactivator or corepressor recruitment. Taken together, we thus proposed a molecular model of RXR repression on the tetramer.
 
Structural basis for retinoic X receptor repression on the tetramer.,Zhang H, Chen L, Chen J, Jiang H, Shen X J Biol Chem. 2011 May 24. PMID:21613212<ref>PMID:21613212</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3r2a" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Retinoid X receptor|Retinoid X receptor]]
*[[Nuclear receptor corepressor|Nuclear receptor corepressor]]
*[[Retinoid X receptor 3D structures|Retinoid X receptor 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Chen, J]]
[[Category: Large Structures]]
[[Category: Chen, L]]
[[Category: Chen J]]
[[Category: Jiang, H]]
[[Category: Chen L]]
[[Category: Shen, X]]
[[Category: Jiang H]]
[[Category: Zhang, H]]
[[Category: Shen X]]
[[Category: Ligand-binding domain]]
[[Category: Zhang H]]
[[Category: Nuclear receptor]]
[[Category: Transcription]]
[[Category: Transcription factor]]

Latest revision as of 15:07, 14 March 2024

Crystal structure of RXRalpha ligand-binding domain complexed with corepressor SMRT2 and antagonist rheinCrystal structure of RXRalpha ligand-binding domain complexed with corepressor SMRT2 and antagonist rhein

Structural highlights

3r2a is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 3Å
Ligands:
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]

See Also

References

  1. ↑ 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
  2. ↑ 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
  3. ↑ 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
  4. ↑ 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

3r2a, resolution 3.00Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA
Retrieved from "https://proteopedia.openfox.io/wiki/index.php?title=3r2a&oldid=4096309"