5z12

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Current revision (10:26, 27 March 2024) (edit) (undo)
 
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<StructureSection load='5z12' size='340' side='right'caption='[[5z12]], [[Resolution|resolution]] 2.75&Aring;' scene=''>
<StructureSection load='5z12' size='340' side='right'caption='[[5z12]], [[Resolution|resolution]] 2.75&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[5z12]] is a 8 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=5Z12 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5Z12 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[5z12]] is a 8 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=5Z12 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5Z12 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=33Y:1-METHYLETHYL+3-[(3,4-DIFLUOROPHENYL)CARBONYL]-1,1-DIMETHYL-1,2,3,6-TETRAHYDROAZEPINO[4,5-B]INDOLE-5-CARBOXYLATE'>33Y</scene>, <scene name='pdbligand=9CR:(9CIS)-RETINOIC+ACID'>9CR</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.75&#8491;</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NR1H4, BAR, FXR, HRR1, RIP14 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), RXRA, NR2B1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=33Y:1-METHYLETHYL+3-[(3,4-DIFLUOROPHENYL)CARBONYL]-1,1-DIMETHYL-1,2,3,6-TETRAHYDROAZEPINO[4,5-B]INDOLE-5-CARBOXYLATE'>33Y</scene>, <scene name='pdbligand=9CR:(9CIS)-RETINOIC+ACID'>9CR</scene></td></tr>
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<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=5z12 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5z12 OCA], [http://pdbe.org/5z12 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5z12 RCSB], [http://www.ebi.ac.uk/pdbsum/5z12 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5z12 ProSAT]</span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5z12 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5z12 OCA], [https://pdbe.org/5z12 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5z12 RCSB], [https://www.ebi.ac.uk/pdbsum/5z12 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5z12 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/NR1H4_HUMAN NR1H4_HUMAN]] Ligand-activated transcription factor. Receptor for bile acids such as chenodeoxycholic acid, lithocholic acid and deoxycholic acid. Represses the transcription of the cholesterol 7-alpha-hydroxylase gene (CYP7A1) through the induction of NR0B2 or FGF19 expression, via two distinct mechanisms. Activates the intestinal bile acid-binding protein (IBABP). Activates the transcription of bile salt export pump ABCB11 by directly recruiting histone methyltransferase CARM1 to this locus.<ref>PMID:10334992</ref> <ref>PMID:10334993</ref> <ref>PMID:12815072</ref> <ref>PMID:15471871</ref> <ref>PMID:12718892</ref> <ref>PMID:18621523</ref> <ref>PMID:19410460</ref> <ref>PMID:19586769</ref> [[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>
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[https://www.uniprot.org/uniprot/NR1H4_HUMAN NR1H4_HUMAN] Ligand-activated transcription factor. Receptor for bile acids such as chenodeoxycholic acid, lithocholic acid and deoxycholic acid. Represses the transcription of the cholesterol 7-alpha-hydroxylase gene (CYP7A1) through the induction of NR0B2 or FGF19 expression, via two distinct mechanisms. Activates the intestinal bile acid-binding protein (IBABP). Activates the transcription of bile salt export pump ABCB11 by directly recruiting histone methyltransferase CARM1 to this locus.<ref>PMID:10334992</ref> <ref>PMID:10334993</ref> <ref>PMID:12815072</ref> <ref>PMID:15471871</ref> <ref>PMID:12718892</ref> <ref>PMID:18621523</ref> <ref>PMID:19410460</ref> <ref>PMID:19586769</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Farnesoid X receptor (FXR) is a member of the family of ligand-activated nuclear receptors. FXR plays critical roles in maintaining many metabolic pathways, including bile acid regulation and glucose and lipid homeostasis, and forms a heterodimeric complex with the retinoid X receptor (RXR). Despite the important roles of the FXR/RXR heterodimerization in human physiology, the molecular basis underlying the FXR/RXR interaction is still uncertain in the absence of a complex structure. Here, we report the heterodimeric structure of FXR and RXR in the presence of an FXR agonist (WAY-362450), RXR agonist (9-cis retinoic acid), and a peptide derived from steroid receptor coactivator (SRC2), revealing both unique and conserved modes for FXR heterodimerization. We found that the dimerization with RXR induced allosteric conformational changes on the coactivator binding site of FXR. These changes enhanced the transcriptional activity of FXR by promoting the coactivator binding, thus suggesting a structural basis for the functional permissiveness of the FXR/RXR heterodimer complex. Furthermore, sequence analyses together with functional mutagenesis studies indicated that the helix H10 largely responsible for the dimerization is highly conserved and also critical for the FXR transcriptional activity. Our findings highlight the important roles of RXR heterodimerization in the nuclear receptor signaling, providing a potential framework to develop pharmaceutical agents in treating the FXR/RXR related diseases.
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Structural insights into the heterodimeric complex of the nuclear receptors FXR and RXR.,Zheng W, Lu Y, Tian S, Ma F, Wei Y, Xu S, Li Y J Biol Chem. 2018 Jun 22. pii: RA118.004188. doi: 10.1074/jbc.RA118.004188. PMID:29934308<ref>PMID:29934308</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 5z12" style="background-color:#fffaf0;"></div>
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==See Also==
==See Also==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Li, Y]]
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[[Category: Li Y]]
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[[Category: Lu, Y]]
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[[Category: Lu Y]]
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[[Category: Complex]]
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[[Category: Nuclear protein]]
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Current revision

A structure of FXR/RXR

PDB ID 5z12

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Proteopedia Page Contributors and Editors (what is this?)

OCA

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