4dor

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==Human Nuclear Receptor Liver Receptor Homologue-1, LRH-1, in its apo State Bound to a Fragment of Human SHP Box1==
==Human Nuclear Receptor Liver Receptor Homologue-1, LRH-1, in its apo State Bound to a Fragment of Human SHP Box1==
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<StructureSection load='4dor' size='340' side='right' caption='[[4dor]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
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<StructureSection load='4dor' size='340' side='right'caption='[[4dor]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4dor]] 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=4DOR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DOR FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4dor]] is a 4 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=4DOR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DOR 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=EPH:L-ALPHA-PHOSPHATIDYL-BETA-OLEOYL-GAMMA-PALMITOYL-PHOSPHATIDYLETHANOLAMINE'>EPH</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]] 1.9&#8491;</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">B1F, CPF, FTF, LRH-1, NR5A2 ([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=EPH:L-ALPHA-PHOSPHATIDYL-BETA-OLEOYL-GAMMA-PALMITOYL-PHOSPHATIDYLETHANOLAMINE'>EPH</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=4dor FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dor OCA], [http://pdbe.org/4dor PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4dor RCSB], [http://www.ebi.ac.uk/pdbsum/4dor PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4dor 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=4dor FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dor OCA], [https://pdbe.org/4dor PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dor RCSB], [https://www.ebi.ac.uk/pdbsum/4dor PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dor ProSAT]</span></td></tr>
</table>
</table>
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== Disease ==
 
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[[http://www.uniprot.org/uniprot/NR0B2_HUMAN NR0B2_HUMAN]] Defects in NR0B2 may be associated with obesity (OBESITY) [MIM:[http://omim.org/entry/601665 601665]]. It is a condition characterized by an increase of body weight beyond the limitation of skeletal and physical requirements, as the result of excessive accumulation of body fat.<ref>PMID:11136233</ref>
 
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/NR5A2_HUMAN NR5A2_HUMAN]] Binds to the sequence element 5'-AACGACCGACCTTGAG-3' of the enhancer II of hepatitis B virus genes, a critical cis-element of their expression and regulation. May be responsible for the liver-specific activity of enhancer II, probably in combination with other hepatocyte transcription factors. Key regulator of cholesterol 7-alpha-hydroxylase gene (CYP7A) expression in liver. May also contribute to the regulation of pancreas-specific genes and play important roles in embryonic development. [[http://www.uniprot.org/uniprot/NR0B2_HUMAN NR0B2_HUMAN]] Acts as a transcriptional regulator. Acts as a negative regulator of receptor-dependent signaling pathways. Specifically inhibits transactivation of the nuclear receptor with whom it interacts. Inhibits transcriptional activity of NEUROD1 on E-box-containing promoter by interfering with the coactivation function of the p300/CBP-mediated trancription complex for NEUROD1.<ref>PMID:14752053</ref>
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[https://www.uniprot.org/uniprot/NR5A2_HUMAN NR5A2_HUMAN] Binds to the sequence element 5'-AACGACCGACCTTGAG-3' of the enhancer II of hepatitis B virus genes, a critical cis-element of their expression and regulation. May be responsible for the liver-specific activity of enhancer II, probably in combination with other hepatocyte transcription factors. Key regulator of cholesterol 7-alpha-hydroxylase gene (CYP7A) expression in liver. May also contribute to the regulation of pancreas-specific genes and play important roles in embryonic development.
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The human nuclear receptor liver receptor homolog-1 (LRH-1) has an important role in controlling lipid and cholesterol homeostasis and is a potential target for the treatment of diabetes and hepatic diseases. LRH-1 is known to bind phospholipids, but the role of phospholipids in controlling LRH-1 activation remains highly debated. Here we describe the structure of both apo LRH-1 and LRH-1 in complex with the antidiabetic phospholipid dilauroylphosphatidylcholine (DLPC). Together with hydrogen-deuterium exchange MS and functional data, our studies show that DLPC binding is a dynamic process that alters co-regulator selectivity. We show that the lipid-free receptor undergoes previously unrecognized structural fluctuations, allowing it to interact with widely expressed co-repressors. These observations enhance our understanding of LRH-1 regulation and highlight its importance as a new therapeutic target for controlling diabetes.
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Antidiabetic phospholipid-nuclear receptor complex reveals the mechanism for phospholipid-driven gene regulation.,Musille PM, Pathak MC, Lauer JL, Hudson WH, Griffin PR, Ortlund EA Nat Struct Mol Biol. 2012 Apr 15;19(5):532-7. doi: 10.1038/nsmb.2279. PMID:22504882<ref>PMID:22504882</ref>
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==See Also==
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*[[Liver receptor homolog-1|Liver receptor homolog-1]]
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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 4dor" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
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[[Category: Homo sapiens]]
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[[Category: Musille, P M]]
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[[Category: Large Structures]]
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[[Category: Ortlund, E A]]
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[[Category: Musille PM]]
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[[Category: Diabetes]]
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[[Category: Ortlund EA]]
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[[Category: Ligand binding domain]]
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[[Category: Nr5a]]
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[[Category: Nuclear receptor]]
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[[Category: Phosphatidylcholine]]
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[[Category: Phospholipid]]
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[[Category: Transcription]]
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Current revision

Human Nuclear Receptor Liver Receptor Homologue-1, LRH-1, in its apo State Bound to a Fragment of Human SHP Box1

PDB ID 4dor

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