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| | <StructureSection load='1xiu' size='340' side='right'caption='[[1xiu]], [[Resolution|resolution]] 2.50Å' scene=''> | | <StructureSection load='1xiu' size='340' side='right'caption='[[1xiu]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1xiu]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Australorbis_glabratus Australorbis glabratus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XIU OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1XIU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1xiu]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Biomphalaria_glabrata Biomphalaria glabrata] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XIU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1XIU FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9CR:(9CIS)-RETINOIC+ACID'>9CR</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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1fby|1fby]], [[1lbd|1lbd]], [[1g1u|1g1u]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9CR:(9CIS)-RETINOIC+ACID'>9CR</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RXR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=6526 Australorbis glabratus])</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=1xiu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xiu OCA], [https://pdbe.org/1xiu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1xiu RCSB], [https://www.ebi.ac.uk/pdbsum/1xiu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1xiu ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histone_acetyltransferase Histone acetyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.48 2.3.1.48] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1xiu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xiu OCA], [http://pdbe.org/1xiu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1xiu RCSB], [http://www.ebi.ac.uk/pdbsum/1xiu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1xiu ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| - | == Disease == | |
| - | [[http://www.uniprot.org/uniprot/NCOA1_HUMAN NCOA1_HUMAN]] Note=A chromosomal aberration involving NCOA1 is a cause of rhabdomyosarcoma. Translocation t(2;2)(q35;p23) with PAX3 generates the NCOA1-PAX3 oncogene consisting of the N-terminus part of PAX3 and the C-terminus part of NCOA1. The fusion protein acts as a transcriptional activator. Rhabdomyosarcoma is the most common soft tissue carcinoma in childhood, representing 5-8% of all malignancies in children. | |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/NCOA1_HUMAN NCOA1_HUMAN]] Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. Involved in the coactivation of different nuclear receptors, such as for steroids (PGR, GR and ER), retinoids (RXRs), thyroid hormone (TRs) and prostanoids (PPARs). Also involved in coactivation mediated by STAT3, STAT5A, STAT5B and STAT6 transcription factors. Displays histone acetyltransferase activity toward H3 and H4; the relevance of such activity remains however unclear. Plays a central role in creating multisubunit coactivator complexes that act via remodeling of chromatin, and possibly acts by participating in both chromatin remodeling and recruitment of general transcription factors. Required with NCOA2 to control energy balance between white and brown adipose tissues. Required for mediating steroid hormone response. Isoform 2 has a higher thyroid hormone-dependent transactivation activity than isoform 1 and isoform 3.<ref>PMID:9427757</ref> <ref>PMID:7481822</ref> <ref>PMID:9223431</ref> <ref>PMID:9296499</ref> <ref>PMID:9223281</ref> <ref>PMID:10449719</ref> <ref>PMID:12954634</ref> | + | [https://www.uniprot.org/uniprot/RXR_BIOGL RXR_BIOGL] Ligand-dependent transcription factor probably involved in the retinoic acid response pathway. Binds 9-cis-retinoic acid (9C-RA) and, to a lesser extent, docosahexaenoic acid (DHA), phytanic acid, methoprene acid and oleic acid. Binds to double-stranded DNA sequences containing direct repeats (DR) with the consensus sequence 5'-[AG]GGTCA-3' and 1, 2, 3, 4 or 5 nucleotides in between (DR1, DR2, DR3. DR4 and DR5, respectively). Binding to DR1 is strongest. Transactivates gene expression when 9C-RA or DHA is bound.<ref>PMID:15821117</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: Australorbis glabratus]] | + | [[Category: Biomphalaria glabrata]] |
| - | [[Category: Histone acetyltransferase]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Borel, F]] | + | [[Category: Borel F]] |
| - | [[Category: Ferrer, J L]] | + | [[Category: De Groot A]] |
| - | [[Category: Fontecilla-Camps, J C]] | + | [[Category: De Rosny E]] |
| - | [[Category: Groot, A De]]
| + | [[Category: Ferrer J-L]] |
| - | [[Category: Juillan-Binard, C]] | + | [[Category: Fontecilla-Camps J-C]] |
| - | [[Category: Laudet, V]] | + | [[Category: Juillan-Binard C]] |
| - | [[Category: Pebay-Peroula, E]]
| + | [[Category: Laudet V]] |
| - | [[Category: Rosny, E De]] | + | [[Category: Pebay-Peroula E]] |
| - | [[Category: Nuclear receptor]]
| + | |
| - | [[Category: Protein-ligand complex]]
| + | |
| - | [[Category: Retinoid receptor]] | + | |
| - | [[Category: Transcription-transferase complex]] | + | |
| Structural highlights
Function
RXR_BIOGL Ligand-dependent transcription factor probably involved in the retinoic acid response pathway. Binds 9-cis-retinoic acid (9C-RA) and, to a lesser extent, docosahexaenoic acid (DHA), phytanic acid, methoprene acid and oleic acid. Binds to double-stranded DNA sequences containing direct repeats (DR) with the consensus sequence 5'-[AG]GGTCA-3' and 1, 2, 3, 4 or 5 nucleotides in between (DR1, DR2, DR3. DR4 and DR5, respectively). Binding to DR1 is strongest. Transactivates gene expression when 9C-RA or DHA is bound.[1]
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
Nuclear receptors form an important class of transcription regulators in metazoans. To learn more about the evolution of these proteins, we have initiated structural studies on nuclear receptor ligand-binding domains from various animals. Here we present the crystal structure of the ligand-binding domain (LBD) of the retinoid X receptor (RXR) from the mollusc Biomphalaria glabrata. The structure reveals a novel tetrameric association in which each monomer is complexed to the human RXR ligand 9-cis retinoic acid and to a human co-activator-derived peptide. The ligand and the co-activator peptide are bound in essentially the same manner as observed in previously reported human RXR LBD structures, suggesting that the mechanisms of RXR-mediated transcription regulation are very similar in mollusc and human. The structure shows further that binding of ligand and co-activator peptide does not necessarily lead to the typical holo-conformation in which helix 12 (H12) folds back and packs against the LBD. Within a canonical dimer, only one monomer is in this closed agonist conformation. The other monomer is in an open conformation with H12 protruding from the LBD core, occupying the H12 interaction groove of another open monomer in an adjacent dimer in a domain swapping fashion, thus resulting in a tetrameric association. Additional tetramer interfaces are formed between H11 of the closed LBD and H6 of the open LBD. This novel holo-tetramer configuration may have a biological role in activating genes whose promoters are poorly recognised by dimers but much more efficiently by the corresponding tetramers.
Crystal structure of a novel tetrameric complex of agonist-bound ligand-binding domain of Biomphalaria glabrata retinoid X receptor.,de Groot A, de Rosny E, Juillan-Binard C, Ferrer JL, Laudet V, Pierce RJ, Pebay-Peyroula E, Fontecilla-Camps JC, Borel F J Mol Biol. 2005 Dec 9;354(4):841-53. Epub 2005 Oct 21. PMID:16274693[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Bouton D, Escriva H, de Mendonça RL, Glineur C, Bertin B, Noël C, Robinson-Rechavi M, de Groot A, Cornette J, Laudet V, Pierce RJ. A conserved retinoid X receptor (RXR) from the mollusk Biomphalaria glabrata transactivates transcription in the presence of retinoids. J Mol Endocrinol. 2005 Apr;34(2):567-82. PMID:15821117 doi:10.1677/jme.1.01766
- ↑ de Groot A, de Rosny E, Juillan-Binard C, Ferrer JL, Laudet V, Pierce RJ, Pebay-Peyroula E, Fontecilla-Camps JC, Borel F. Crystal structure of a novel tetrameric complex of agonist-bound ligand-binding domain of Biomphalaria glabrata retinoid X receptor. J Mol Biol. 2005 Dec 9;354(4):841-53. Epub 2005 Oct 21. PMID:16274693 doi:10.1016/j.jmb.2005.09.090
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