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==Mutual Synergistic Folding in the Interaction Between Nuclear Receptor Coactivators CBP and ACTR==
==Mutual Synergistic Folding in the Interaction Between Nuclear Receptor Coactivators CBP and ACTR==
<StructureSection load='1kbh' size='340' side='right'caption='[[1kbh]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
<StructureSection load='1kbh' size='340' side='right'caption='[[1kbh]]' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1kbh]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human] and [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. The February 2010 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Enhanceosome''  by David Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2010_2 10.2210/rcsb_pdb/mom_2010_2]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KBH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1KBH FirstGlance]. <br>
<table><tr><td colspan='2'>[[1kbh]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. The February 2010 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Enhanceosome''  by David Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2010_2 10.2210/rcsb_pdb/mom_2010_2]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KBH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1KBH FirstGlance]. <br>
</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ACTR ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), CBP ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=1kbh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1kbh OCA], [https://pdbe.org/1kbh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1kbh RCSB], [https://www.ebi.ac.uk/pdbsum/1kbh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1kbh 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=1kbh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1kbh OCA], [https://pdbe.org/1kbh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1kbh RCSB], [https://www.ebi.ac.uk/pdbsum/1kbh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1kbh ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[https://www.uniprot.org/uniprot/NCOA3_HUMAN NCOA3_HUMAN]] Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. Plays a central role in creating a multisubunit coactivator complex, which probably acts via remodeling of chromatin. Involved in the coactivation of different nuclear receptors, such as for steroids (GR and ER), retinoids (RARs and RXRs), thyroid hormone (TRs), vitamin D3 (VDR) and prostanoids (PPARs). Displays histone acetyltransferase activity. Also involved in the coactivation of the NF-kappa-B pathway via its interaction with the NFKB1 subunit. Interacts with PSMB9. [[https://www.uniprot.org/uniprot/CBP_MOUSE CBP_MOUSE]] Acetylates histones, giving a specific tag for transcriptional activation. Also acetylates non-histone proteins, like NCOA3 and FOXO1. Binds specifically to phosphorylated CREB and enhances its transcriptional activity toward cAMP-responsive genes. Acts as a coactivator of ALX1 in the presence of EP300 (By similarity).<ref>PMID:10207073</ref> <ref>PMID:11701890</ref> <ref>PMID:15220471</ref> <ref>PMID:16287980</ref> 
[https://www.uniprot.org/uniprot/NCOA3_HUMAN NCOA3_HUMAN] Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. Plays a central role in creating a multisubunit coactivator complex, which probably acts via remodeling of chromatin. Involved in the coactivation of different nuclear receptors, such as for steroids (GR and ER), retinoids (RARs and RXRs), thyroid hormone (TRs), vitamin D3 (VDR) and prostanoids (PPARs). Displays histone acetyltransferase activity. Also involved in the coactivation of the NF-kappa-B pathway via its interaction with the NFKB1 subunit. Interacts with PSMB9.
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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</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=1kbh 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=1kbh ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Nuclear hormone receptors are ligand-activated transcription factors that regulate the expression of genes that are essential for development, reproduction and homeostasis. The hormone response is mediated through recruitment of p160 receptor coactivators and the general transcriptional coactivator CBP/p300, which function synergistically to activate transcription. These coactivators exhibit intrinsic histone acetyltransferase activity, function in the remodelling of chromatin, and facilitate the recruitment of RNA polymerase II and the basal transcription machinery. The activities of the p160 coactivators are dependent on CBP. Both coactivators are essential for proper cell-cycle control, differentiation and apoptosis, and are implicated in cancer and other diseases. To elucidate the molecular basis of assembling the multiprotein activation complex, we undertook a structural and thermodynamic analysis of the interaction domains of CBP and the activator for thyroid hormone and retinoid receptors. Here we show that although the isolated domains are intrinsically disordered, they combine with high affinity to form a cooperatively folded helical heterodimer. Our study uncovers a unique mechanism, called 'synergistic folding', through which p160 coactivators recruit CBP/p300 to allow transmission of the hormonal signal to the transcriptional machinery.
Mutual synergistic folding in recruitment of CBP/p300 by p160 nuclear receptor coactivators.,Demarest SJ, Martinez-Yamout M, Chung J, Chen H, Xu W, Dyson HJ, Evans RM, Wright PE Nature. 2002 Jan 31;415(6871):549-53. PMID:11823864<ref>PMID:11823864</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1kbh" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[CREB-binding protein 3D structures|CREB-binding protein 3D structures]]
*[[CREB-binding protein 3D structures|CREB-binding protein 3D structures]]
*[[Nuclear receptor coactivator|Nuclear receptor coactivator]]
*[[Nuclear receptor coactivator|Nuclear receptor coactivator]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Enhanceosome]]
[[Category: Enhanceosome]]
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Lk3 transgenic mice]]
[[Category: Mus musculus]]
[[Category: RCSB PDB Molecule of the Month]]
[[Category: RCSB PDB Molecule of the Month]]
[[Category: Chen, H]]
[[Category: Chen H]]
[[Category: Chung, J]]
[[Category: Chung J]]
[[Category: Demarest, S J]]
[[Category: Demarest SJ]]
[[Category: Dyson, H J]]
[[Category: Dyson HJ]]
[[Category: Evans, R M]]
[[Category: Evans RM]]
[[Category: Martinez-Yamout, M]]
[[Category: Martinez-Yamout M]]
[[Category: Wright, P E]]
[[Category: Wright PE]]
[[Category: Xu, W]]
[[Category: Xu W]]
[[Category: Actr]]
[[Category: Cbp]]
[[Category: Coactivator]]
[[Category: Creb-binding protein]]
[[Category: Nuclear hormone receptor]]
[[Category: P160]]
[[Category: P300]]
[[Category: Transcription]]

Revision as of 10:59, 3 April 2024

Mutual Synergistic Folding in the Interaction Between Nuclear Receptor Coactivators CBP and ACTRMutual Synergistic Folding in the Interaction Between Nuclear Receptor Coactivators CBP and ACTR

Structural highlights

1kbh is a 2 chain structure with sequence from Homo sapiens and Mus musculus. The February 2010 RCSB PDB Molecule of the Month feature on Enhanceosome by David Goodsell is 10.2210/rcsb_pdb/mom_2010_2. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Solution NMR
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

NCOA3_HUMAN Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. Plays a central role in creating a multisubunit coactivator complex, which probably acts via remodeling of chromatin. Involved in the coactivation of different nuclear receptors, such as for steroids (GR and ER), retinoids (RARs and RXRs), thyroid hormone (TRs), vitamin D3 (VDR) and prostanoids (PPARs). Displays histone acetyltransferase activity. Also involved in the coactivation of the NF-kappa-B pathway via its interaction with the NFKB1 subunit. Interacts with PSMB9.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

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