View source for 5unj


==Structure of Human Liver Receptor Homolog 1 in complex with PGC1a and RJW100==
<StructureSection load='5unj' size='340' side='right'caption='[[5unj]], [[Resolution|resolution]] 1.96&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5unj]] is a 2 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=5UNJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5UNJ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.959&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=RJW:(1R,3AR,6AR)-5-HEXYL-4-PHENYL-3A-(1-PHENYLETHENYL)-1,2,3,3A,6,6A-HEXAHYDROPENTALEN-1-OL'>RJW</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=5unj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5unj OCA], [https://pdbe.org/5unj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5unj RCSB], [https://www.ebi.ac.uk/pdbsum/5unj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5unj ProSAT]</span></td></tr>
</table>
== 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;">
== Publication Abstract from PubMed ==
Peroxisome proliferator-activated gamma coactivator 1-alpha (PGC1alpha) regulates energy metabolism by directly interacting with transcription factors to modulate gene expression. Among the PGC1alpha binding partners is Liver receptor homolog 1 (LRH-1; NR5A2), an orphan nuclear hormone receptor that controls lipid and glucose homeostasis. Although PGC1alpha is known to bind and activate LRH-1, mechanisms through which PGC1alpha changes LRH-1 conformation to drive transcription are unknown. Here, we used biochemical and structural methods to interrogate the LRH-1-PGC1alpha complex. Purified, full-length LRH-1, as well as isolated ligand binding domain, bound to PGC1alpha with higher affinity than to the coactivator, Nuclear Receptor Coactivator-2 (Tif2) in coregulator peptide recruitment assays. We present the first crystal structure of the LRH-1-PGC1alpha complex, which depicts several hydrophobic contacts and a strong charge clamp at the interface between these partners. In molecular dynamics simulations, PGC1alpha induced correlated atomic motion throughout the entire LRH-1 activation function surface, which was dependent on charge clamp formation. In contrast, Tif2 induced weaker signaling at the activation function surface than PGC1alpha but promoted allosteric signaling from the Helix 6/beta-sheet region of LRH-1 to the activation function surface. These studies are the first to probe mechanisms underlying the LRH-1-PGC1alpha interaction and may illuminate strategies for selective therapeutic targeting of PGC1alpha-dependent LRH-1 signaling pathways.

Structure and Dynamics of the Liver Receptor Homolog 1-PGC1alpha Complex.,Mays SG, Okafor CD, Tuntland ML, Whitby RJ, Dharmarajan V, Stec J, Griffin PR, Ortlund EA Mol Pharmacol. 2017 Mar 31. pii: mol.117.108514. doi: 10.1124/mol.117.108514. PMID:28363985<ref>PMID:28363985</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5unj" style="background-color:#fffaf0;"></div>

==See Also==
*[[Liver receptor homolog-1|Liver receptor homolog-1]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Mays SG]]
[[Category: Ortlund EA]]