7aos
From Proteopedia
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| - | ==== | + | ==crystal structure of the RARalpha/RXRalpha ligand binding domain heterodimer in complex with a fragment of SRC1 coactivator== |
| - | <StructureSection load='7aos' size='340' side='right'caption='[[7aos]]' scene=''> | + | <StructureSection load='7aos' size='340' side='right'caption='[[7aos]], [[Resolution|resolution]] 2.55Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7aos]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AOS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AOS FirstGlance]. <br> |
| - | </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=7aos FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7aos OCA], [https://pdbe.org/7aos PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7aos RCSB], [https://www.ebi.ac.uk/pdbsum/7aos PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7aos ProSAT]</span></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]] 2.55Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EQN:4-{[(5,5,8,8-TETRAMETHYL-5,6,7,8-TETRAHYDRONAPHTHALEN-2-YL)CARBONYL]AMINO}BENZOIC+ACID'>EQN</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=LG2:6-[1-(3,5,5,8,8-PENTAMETHYL-5,6,7,8-TETRAHYDRONAPHTHALEN-2-YL)CYCLOPROPYL]PYRIDINE-3-CARBOXYLIC+ACID'>LG2</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=7aos FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7aos OCA], [https://pdbe.org/7aos PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7aos RCSB], [https://www.ebi.ac.uk/pdbsum/7aos PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7aos ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/RXRA_MOUSE RXRA_MOUSE] Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. The high affinity ligand for RXRs is 9-cis retinoic acid. RXRA serves as a common heterodimeric partner for a number of nuclear receptors. The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone acetylation, chromatin condensation and transcriptional suppression. On ligand binding, the corepressors dissociate from the receptors and associate with the coactivators leading to transcriptional activation. The RXRA/PPARA heterodimer is required for PPARA transcriptional activity on fatty acid oxidation genes such as ACOX1 and the P450 system genes.<ref>PMID:1310259</ref> <ref>PMID:10383391</ref> <ref>PMID:12032153</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Retinoic acid receptors (RARs) and retinoid X receptors (RXRs) form heterodimers that activate target gene transcription by recruiting co-activator complexes in response to ligand binding. The nuclear receptor (NR) co-activator TIF2 mediates this recruitment by interacting with the ligand-binding domain (LBD) of NRs trough the nuclear receptor interaction domain (TIF2(NRID)) containing three highly conserved alpha-helical LxxLL motifs (NR-boxes). The precise binding mode of this domain to RXR/RAR is not clear due to the disordered nature of TIF2. Here we present the structural characterization of TIF2(NRID) by integrating several experimental (NMR, SAXS, Far-UV CD, SEC-MALS) and computational data. Collectively, the data are in agreement with a largely disordered protein with partially structured regions, including the NR-boxes and their flanking regions, which are evolutionary conserved. NMR and X-ray crystallographic data on TIF2(NRID) in complex with RXR/RAR reveal a multisite binding of the three NR-boxes as well as an active role of their flanking regions in the interaction. | ||
| + | |||
| + | Structural Insights into the Interaction of the Intrinsically Disordered Co-activator TIF2 with Retinoic Acid Receptor Heterodimer (RXR/RAR).,Senicourt L, le Maire A, Allemand F, Carvalho JE, Guee L, Germain P, Schubert M, Bernado P, Bourguet W, Sibille N J Mol Biol. 2021 Apr 30;433(9):166899. doi: 10.1016/j.jmb.2021.166899. Epub 2021 , Feb 27. PMID:33647291<ref>PMID:33647291</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7aos" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Retinoic acid receptor 3D structures|Retinoic acid receptor 3D structures]] | ||
| + | *[[Retinoid X receptor 3D structures|Retinoid X receptor 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Mus musculus]] |
| + | [[Category: Bourguet W]] | ||
| + | [[Category: Guee L]] | ||
| + | [[Category: Le Maire A]] | ||
Current revision
crystal structure of the RARalpha/RXRalpha ligand binding domain heterodimer in complex with a fragment of SRC1 coactivator
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