3d24: Difference between revisions

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-[[Image:3d24.jpg|left|200px]]
-<!--
+==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)==
-The line below this paragraph, containing "STRUCTURE_3d24", creates the "Structure Box" on the page.
+<StructureSection load='3d24' size='340' side='right'caption='[[3d24]], [[Resolution|resolution]] 2.11&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<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>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.11&#8491;</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>
-{{STRUCTURE_3d24|  PDB=3d24  |  SCENE=  }}
+</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 ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <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>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </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/main_output.php?pdb_ID=3d24 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== 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.
-'''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)'''
+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<ref>PMID:18441008</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 3d24" style="background-color:#fffaf0;"></div>
-==Overview==
+==See Also==
-While 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 (ER) alpha, for example, interacts only with a region of peroxisome proliferator-activated receptor coactivator (PGC)-1alpha that contains the canonical LXXLL motif (NR box2), whereas the LBD of estrogen-related receptor (ERR)alpha binds also 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, while 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 form 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 show that these contacts are functionally relevant and required for efficient ERRalpha/PGC-1alpha interaction. Furthermore, a structure comparison between ERRalpha and ERalpha and mutation analyses provide 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 reveal 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.
+*[[Estrogen-related receptor 3D structures|Estrogen-related receptor 3D structures]]
+== References ==
-==About this Structure==
+<references/>
-D24 is a [[Protein complex]] structure of sequences 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].
+__TOC__
+</StructureSection>
-==Reference==
-Communication between the ERR alpha homodimer interface and the PGC-1alpha binding surface vie the helix 8-9 loop., Greschik H, Althage M, Flaig R, Sato Y, Peluso-Iltis C, Chavant V, Choulier L, Cronet P, Rochel N, Schule R, Stromstedt PE, Moras D, J Biol Chem. 2008 Apr 25;. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18441008 18441008]
 [[Category: Homo sapiens]]
-[[Category: Protein complex]]
+[[Category: Large Structures]]
-[[Category: Flaig, R.]]
+[[Category: Flaig R]]
-[[Category: Greschik, H.]]
+[[Category: Greschik H]]
-[[Category: Moras, D.]]
+[[Category: Moras D]]
-[[Category: Rochel, N.]]
+[[Category: Rochel N]]
-[[Category: SPINE, Structural Proteomics in Europe.]]
+[[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: Polymorphism]]
-[[Category: Rna-binding]]
-[[Category: Spine]]
-[[Category: Structural genomic]]
-[[Category: Structural proteomics in europe]]
-[[Category: Transcription]]
-[[Category: Transcription regulation]]
-[[Category: Zinc]]
-[[Category: Zinc-finger]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jun 11 10:50:58 2008''