|
|
| Line 3: |
Line 3: |
| | <StructureSection load='5unj' size='340' side='right'caption='[[5unj]], [[Resolution|resolution]] 1.96Å' scene=''> | | <StructureSection load='5unj' size='340' side='right'caption='[[5unj]], [[Resolution|resolution]] 1.96Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5unj]] is a 2 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=5UNJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UNJ FirstGlance]. <br> | + | <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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.959Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NR5A2, B1F, CPF, FTF ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5unj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5unj OCA], [http://pdbe.org/5unj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5unj RCSB], [http://www.ebi.ac.uk/pdbsum/5unj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5unj ProSAT]</span></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> | | </table> |
| | == Function == | | == Function == |
| - | [[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. | + | [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 == |
| Line 26: |
Line 26: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Mays, S G]] | + | [[Category: Mays SG]] |
| - | [[Category: Ortlund, E A]] | + | [[Category: Ortlund EA]] |
| - | [[Category: Agonist]]
| + | |
| - | [[Category: Coregulator]]
| + | |
| - | [[Category: Nuclear protein]]
| + | |
| - | [[Category: Nuclear receptor]]
| + | |
| 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 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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Mays SG, Okafor CD, Tuntland ML, Whitby RJ, Dharmarajan V, Stec J, Griffin PR, Ortlund EA. Structure and Dynamics of the Liver Receptor Homolog 1-PGC1alpha Complex. Mol Pharmacol. 2017 Mar 31. pii: mol.117.108514. doi: 10.1124/mol.117.108514. PMID:28363985 doi:http://dx.doi.org/10.1124/mol.117.108514
|
