4dos: Difference between revisions
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==Human Nuclear Receptor Liver Receptor Homologue-1, LRH-1, Bound to DLPC and a Fragment of TIF-2== | ==Human Nuclear Receptor Liver Receptor Homologue-1, LRH-1, Bound to DLPC and a Fragment of TIF-2== | ||
<StructureSection load='4dos' size='340' side='right' caption='[[4dos]], [[Resolution|resolution]] 2.00Å' scene=''> | <StructureSection load='4dos' size='340' side='right'caption='[[4dos]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4dos]] is a 3 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4dos]] is a 3 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=4DOS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DOS FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=PLC:DIUNDECYL+PHOSPHATIDYL+CHOLINE'>PLC</scene> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=PLC:DIUNDECYL+PHOSPHATIDYL+CHOLINE'>PLC</scene></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=4dos FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dos OCA], [https://pdbe.org/4dos PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dos RCSB], [https://www.ebi.ac.uk/pdbsum/4dos PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dos ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[[ | [[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. | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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</div> | </div> | ||
<div class="pdbe-citations 4dos" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 4dos" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Liver receptor homolog-1|Liver receptor homolog-1]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Musille PM]] | ||
[[Category: | [[Category: Ortlund EA]] | ||
Revision as of 11:32, 21 September 2022
Human Nuclear Receptor Liver Receptor Homologue-1, LRH-1, Bound to DLPC and a Fragment of TIF-2Human Nuclear Receptor Liver Receptor Homologue-1, LRH-1, Bound to DLPC and a Fragment of TIF-2
Structural highlights
Function[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. Publication Abstract from PubMedThe 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. 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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