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| | <StructureSection load='1xb7' size='340' side='right'caption='[[1xb7]], [[Resolution|resolution]] 2.50Å' scene=''> | | <StructureSection load='1xb7' size='340' side='right'caption='[[1xb7]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1xb7]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XB7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1XB7 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1xb7]] 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=1XB7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1XB7 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IOD:IODIDE+ION'>IOD</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]] 2.5Å</td></tr> |
| | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IOD:IODIDE+ION'>IOD</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=1xb7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xb7 OCA], [https://pdbe.org/1xb7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1xb7 RCSB], [https://www.ebi.ac.uk/pdbsum/1xb7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1xb7 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=1xb7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xb7 OCA], [https://pdbe.org/1xb7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1xb7 RCSB], [https://www.ebi.ac.uk/pdbsum/1xb7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1xb7 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/ERR1_HUMAN ERR1_HUMAN]] Binds to an ERR-alpha response element (ERRE) containing a single consensus half-site, 5'-TNAAGGTCA-3'. Can bind to the medium-chain acyl coenzyme A dehydrogenase (MCAD) response element NRRE-1 and may act as an important regulator of MCAD promoter. Binds to the C1 region of the lactoferrin gene promoter. Requires dimerization and the coactivator, PGC-1A, for full activity. The ERRalpha/PGC1alpha complex is a regulator of energy metabolism.<ref>PMID:9271417</ref> <ref>PMID:12522104</ref> <ref>PMID:16150865</ref> <ref>PMID:17676930</ref> <ref>PMID:18063693</ref> [[https://www.uniprot.org/uniprot/PRGC1_HUMAN PRGC1_HUMAN]] Transcriptional coactivator for steroid receptors and nuclear receptors. Greatly increases the transcriptional activity of PPARG and thyroid hormone receptor on the uncoupling protein promoter. Can regulate key mitochondrial genes that contribute to the program of adaptive thermogenesis. Plays an essential role in metabolic reprogramming in response to dietary availability through coordination of the expression of a wide array of genes involved in glucose and fatty acid metabolism.<ref>PMID:10713165</ref> <ref>PMID:20005308</ref> <ref>PMID:21376232</ref>
| + | [https://www.uniprot.org/uniprot/ERR1_HUMAN ERR1_HUMAN] Binds to an ERR-alpha response element (ERRE) containing a single consensus half-site, 5'-TNAAGGTCA-3'. Can bind to the medium-chain acyl coenzyme A dehydrogenase (MCAD) response element NRRE-1 and may act as an important regulator of MCAD promoter. Binds to the C1 region of the lactoferrin gene promoter. Requires dimerization and the coactivator, PGC-1A, for full activity. The ERRalpha/PGC1alpha complex is a regulator of energy metabolism.<ref>PMID:9271417</ref> <ref>PMID:12522104</ref> <ref>PMID:16150865</ref> <ref>PMID:17676930</ref> <ref>PMID:18063693</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Bitsch, F]] | + | [[Category: Bitsch F]] |
| - | [[Category: Filipuzzi, I]] | + | [[Category: Filipuzzi I]] |
| - | [[Category: Fournier, B]] | + | [[Category: Fournier B]] |
| - | [[Category: Geiser, M]] | + | [[Category: Geiser M]] |
| - | [[Category: Graham, A]] | + | [[Category: Graham A]] |
| - | [[Category: Kallen, J]] | + | [[Category: Kallen J]] |
| - | [[Category: Riou, V]] | + | [[Category: Riou V]] |
| - | [[Category: Schilb, A]] | + | [[Category: Schilb A]] |
| - | [[Category: Schlaeppi, J M]] | + | [[Category: Schlaeppi JM]] |
| - | [[Category: Strauss, A]] | + | [[Category: Strauss A]] |
| - | [[Category: Amphipathic alpha-helix]]
| + | |
| - | [[Category: Coactivator peptide]]
| + | |
| - | [[Category: Ligand binding domain]]
| + | |
| - | [[Category: Nuclear hormone receptor]]
| + | |
| - | [[Category: Three-layered alpha-helical sandwich]]
| + | |
| - | [[Category: Transcription]]
| + | |
| Structural highlights
Function
ERR1_HUMAN Binds to an ERR-alpha response element (ERRE) containing a single consensus half-site, 5'-TNAAGGTCA-3'. Can bind to the medium-chain acyl coenzyme A dehydrogenase (MCAD) response element NRRE-1 and may act as an important regulator of MCAD promoter. Binds to the C1 region of the lactoferrin gene promoter. Requires dimerization and the coactivator, PGC-1A, for full activity. The ERRalpha/PGC1alpha complex is a regulator of energy metabolism.[1] [2] [3] [4] [5]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The crystal structure of the ligand binding domain (LBD) of the estrogen-related receptor alpha (ERRalpha, NR3B1) complexed with a coactivator peptide from peroxisome proliferator-activated receptor coactivator-1alpha (PGC-1alpha) reveals a transcriptionally active conformation in the absence of a ligand. This is the first x-ray structure of ERRalpha LBD, solved to a resolution of 2.5 A, and the first structure of a PGC-1alpha complex. The putative ligand binding pocket (LBP) of ERRalpha is almost completely occupied by side chains, in particular with the bulky side chain of Phe328 (corresponding to Ala272 in ERRgamma and Ala350 in estrogen receptor alpha). Therefore, a ligand of a size equivalent to more than approximately 4 carbon atoms could only bind in the LBP, if ERRalpha would undergo a major conformational change (in particular the ligand would displace H12 from its agonist position). The x-ray structure thus provides strong evidence for ligand-independent transcriptional activation by ERRalpha. The interactions of PGC-1alpha with ERRalpha also reveal for the first time the atomic details of how a coactivator peptide containing an inverted LXXLL motif (namely a LLXYL motif) binds to a LBD. In addition, we show that a PGC-1alpha peptide containing this nuclear box motif from the L3 site binds ERRalpha LBD with a higher affinity than a peptide containing a steroid receptor coactivator-1 motif and that the affinity is further enhanced when all three leucine-rich regions of PGC-1alpha are present.
Evidence for ligand-independent transcriptional activation of the human estrogen-related receptor alpha (ERRalpha): crystal structure of ERRalpha ligand binding domain in complex with peroxisome proliferator-activated receptor coactivator-1alpha.,Kallen J, Schlaeppi JM, Bitsch F, Filipuzzi I, Schilb A, Riou V, Graham A, Strauss A, Geiser M, Fournier B J Biol Chem. 2004 Nov 19;279(47):49330-7. Epub 2004 Aug 26. PMID:15337744[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Sladek R, Bader JA, Giguere V. The orphan nuclear receptor estrogen-related receptor alpha is a transcriptional regulator of the human medium-chain acyl coenzyme A dehydrogenase gene. Mol Cell Biol. 1997 Sep;17(9):5400-9. PMID:9271417
- ↑ Schreiber SN, Knutti D, Brogli K, Uhlmann T, Kralli A. The transcriptional coactivator PGC-1 regulates the expression and activity of the orphan nuclear receptor estrogen-related receptor alpha (ERRalpha). J Biol Chem. 2003 Mar 14;278(11):9013-8. Epub 2003 Jan 8. PMID:12522104 doi:http://dx.doi.org/10.1074/jbc.M212923200
- ↑ Barry JB, Laganiere J, Giguere V. A single nucleotide in an estrogen-related receptor alpha site can dictate mode of binding and peroxisome proliferator-activated receptor gamma coactivator 1alpha activation of target promoters. Mol Endocrinol. 2006 Feb;20(2):302-10. Epub 2005 Sep 8. PMID:16150865 doi:http://dx.doi.org/me.2005-0313
- ↑ Vu EH, Kraus RJ, Mertz JE. Phosphorylation-dependent sumoylation of estrogen-related receptor alpha1. Biochemistry. 2007 Aug 28;46(34):9795-804. Epub 2007 Aug 4. PMID:17676930 doi:http://dx.doi.org/10.1021/bi700316g
- ↑ Tremblay AM, Wilson BJ, Yang XJ, Giguere V. Phosphorylation-dependent sumoylation regulates estrogen-related receptor-alpha and -gamma transcriptional activity through a synergy control motif. Mol Endocrinol. 2008 Mar;22(3):570-84. Epub 2007 Dec 6. PMID:18063693 doi:me.2007-0357
- ↑ Kallen J, Schlaeppi JM, Bitsch F, Filipuzzi I, Schilb A, Riou V, Graham A, Strauss A, Geiser M, Fournier B. Evidence for ligand-independent transcriptional activation of the human estrogen-related receptor alpha (ERRalpha): crystal structure of ERRalpha ligand binding domain in complex with peroxisome proliferator-activated receptor coactivator-1alpha. J Biol Chem. 2004 Nov 19;279(47):49330-7. Epub 2004 Aug 26. PMID:15337744 doi:10.1074/jbc.M407999200
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