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| | ==Crystal structure of ligand-binding domain of estrogen-related receptor alpha (ERRalpha) in complex with the peroxisome proliferators-activated receptor coactivator-1alpha box3 peptide (PGC-1alpha)== | | ==Crystal structure of ligand-binding domain of estrogen-related receptor alpha (ERRalpha) in complex with the peroxisome proliferators-activated receptor coactivator-1alpha box3 peptide (PGC-1alpha)== |
| - | <StructureSection load='3d24' size='340' side='right' caption='[[3d24]], [[Resolution|resolution]] 2.11Å' scene=''> | + | <StructureSection load='3d24' size='340' side='right'caption='[[3d24]], [[Resolution|resolution]] 2.11Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3d24]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3D24 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3D24 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3d24]] 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=3D24 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3D24 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1xb7|1xb7]]</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]] 2.11Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ESRRA, ERR1, ESRL1, NR3B1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=3d24 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3d24 OCA], [https://pdbe.org/3d24 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3d24 RCSB], [https://www.ebi.ac.uk/pdbsum/3d24 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3d24 ProSAT]</span></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=3d24 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3d24 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3d24 RCSB], [http://www.ebi.ac.uk/pdbsum/3d24 PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == 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> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/d2/3d24_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/d2/3d24_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
| - | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf]. | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3d24 ConSurf]. |
| | <div style="clear:both"></div> | | <div style="clear:both"></div> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 3d24" style="background-color:#fffaf0;"></div> |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Estrogen-related receptor|Estrogen-related receptor]] | + | *[[Estrogen-related receptor 3D structures|Estrogen-related receptor 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Flaig, R]] | + | [[Category: Large Structures]] |
| - | [[Category: Greschik, H]] | + | [[Category: Flaig R]] |
| - | [[Category: Moras, D]] | + | [[Category: Greschik H]] |
| - | [[Category: Rochel, N]] | + | [[Category: Moras D]] |
| - | [[Category: SPINE, Structural Proteomics in Europe]]
| + | [[Category: Rochel N]] |
| - | [[Category: Sato, Y]] | + | [[Category: Sato Y]] |
| - | [[Category: Coactivator]]
| + | |
| - | [[Category: Dna-binding]]
| + | |
| - | [[Category: Ligand binding domain]]
| + | |
| - | [[Category: Metal-binding]]
| + | |
| - | [[Category: Nuclear receptor]]
| + | |
| - | [[Category: Nucleus]]
| + | |
| - | [[Category: Phosphoprotein]]
| + | |
| - | [[Category: Rna-binding]]
| + | |
| - | [[Category: Spine]]
| + | |
| - | [[Category: Structural genomic]]
| + | |
| - | [[Category: Structural proteomics in europe]]
| + | |
| - | [[Category: Transcription]]
| + | |
| - | [[Category: Transcription regulation]]
| + | |
| - | [[Category: Zinc-finger]]
| + | |
| 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
Although structural studies on the ligand-binding domain (LBD) have established the general mode of nuclear receptor (NR)/coactivator interaction, determinants of binding specificity are only partially understood. The LBD of estrogen receptor-alpha (ERalpha), for example, interacts only with a region of peroxisome proliferator-activated receptor coactivator (PGC)-1alpha, which contains the canonical LXXLL motif (NR box2), whereas the LBD of estrogen-related receptor-alpha (ERRalpha) also binds efficiently an untypical, LXXYL-containing region (NR box3) of PGC-1alpha. Surprisingly, in a previous structural study, the ERalpha LBD has been observed to bind NR box3 of transcriptional intermediary factor (TIF)-2 untypically via LXXYL, whereas the ERRalpha LBD binds this region of TIF-2 only poorly. Here we present a new crystal structure of the ERRalpha LBD in complex with a PGC-1alpha box3 peptide. In this structure, residues N-terminal of the PGC-1alpha LXXYL motif formed contacts with helix 4, the loop connecting helices 8 and 9, and with the C terminus of the ERRalpha LBD. Interaction studies using wild-type and mutant PGC-1alpha and ERRalpha showed that these contacts are functionally relevant and are required for efficient ERRalpha/PGC-1alpha interaction. Furthermore, a structure comparison between ERRalpha and ERalpha and mutation analyses provided evidence that the helix 8-9 loop, which differs significantly in both nuclear receptors, is a major determinant of coactivator binding specificity. Finally, our results revealed that in ERRalpha the helix 8-9 loop allosterically links the LBD homodimer interface with the coactivator cleft, thus providing a plausible explanation for distinct PGC-1alpha binding to ERRalpha monomers and homodimers.
Communication between the ERRalpha homodimer interface and the PGC-1alpha binding surface via the helix 8-9 loop.,Greschik H, Althage M, Flaig R, Sato Y, Chavant V, Peluso-Iltis C, Choulier L, Cronet P, Rochel N, Schule R, Stromstedt PE, Moras D J Biol Chem. 2008 Jul 18;283(29):20220-30. Epub 2008 Apr 25. PMID:18441008[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
- ↑ Greschik H, Althage M, Flaig R, Sato Y, Chavant V, Peluso-Iltis C, Choulier L, Cronet P, Rochel N, Schule R, Stromstedt PE, Moras D. Communication between the ERRalpha homodimer interface and the PGC-1alpha binding surface via the helix 8-9 loop. J Biol Chem. 2008 Jul 18;283(29):20220-30. Epub 2008 Apr 25. PMID:18441008 doi:10.1074/jbc.M801920200
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