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2lww

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==NMR structure of RelA-TAD/CBP-TAZ1 complex==
==NMR structure of RelA-TAD/CBP-TAZ1 complex==
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<StructureSection load='2lww' size='340' side='right' caption='[[2lww]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
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<StructureSection load='2lww' size='340' side='right'caption='[[2lww]]' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[2lww]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LWW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2LWW FirstGlance]. <br>
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<table><tr><td colspan='2'>[[2lww]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LWW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LWW FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Crebbp, Cbp ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus]), Rela, mCG_11759 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<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>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2lww FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lww OCA], [https://pdbe.org/2lww PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2lww RCSB], [https://www.ebi.ac.uk/pdbsum/2lww PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2lww ProSAT]</span></td></tr>
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<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=2lww FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lww OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2lww RCSB], [http://www.ebi.ac.uk/pdbsum/2lww PDBsum]</span></td></tr>
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</table>
</table>
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<div style="background-color:#fffaf0;">
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== Function ==
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== Publication Abstract from PubMed ==
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[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>
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NF-kappaB plays a vital role in cellular immune and inflammatory response, survival, and proliferation by regulating the transcription of various genes involved in these processes. To activate transcription, RelA (a prominent NF-kappaB family member) interacts with transcriptional co-activators like CREB-binding protein (CBP) and its paralog p300 in addition to its cognate kappaB sites on the promoter/enhancer regions of DNA. The RelA:CBP/p300 complex is comprised of two components-first, DNA binding domain of RelA interacts with the KIX domain of CBP/p300, and second, the transcriptional activation domain (TAD) of RelA binds to the TAZ1 domain of CBP/p300. A phosphorylation event of a well-conserved RelA(Ser276) is prerequisite for the former interaction to occur and is considered a decisive factor for the overall RelA:CBP/p300 interaction. The role of the latter interaction in the transcription of RelA-activated genes remains unclear. Here we provide the solution structure of the latter component of the RelA:CBP complex by NMR spectroscopy. The structure reveals the folding of RelA-TA2 (a section of TAD) upon binding to TAZ1 through its well-conserved hydrophobic sites in a series of grooves on the TAZ1 surface. The structural analysis coupled with the mechanistic studies by mutational and isothermal calorimetric analyses allowed the design of RelA-mutants that selectively abrogated the two distinct components of the RelA:CBP/p300 interaction. Detailed studies of these RelA mutants using cell-based techniques, mathematical modeling, and genome-wide gene expression analysis showed that a major set of the RelA-activated genes, larger than previously believed, is affected by this interaction. We further show how the RelA:CBP/p300 interaction controls the nuclear response of NF-kappaB through the negative feedback loop of NF-kappaB pathway. Additionally, chromatin analyses of RelA target gene promoters showed constitutive recruitment of CBP/p300, thus indicating a possible role of CBP/p300 in recruitment of RelA to its target promoter sites.
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Analysis of the RelA:CBP/p300 Interaction Reveals Its Involvement in NF-kappaB-Driven Transcription.,Mukherjee SP, Behar M, Birnbaum HA, Hoffmann A, Wright PE, Ghosh G PLoS Biol. 2013 Sep;11(9):e1001647. doi: 10.1371/journal.pbio.1001647. Epub 2013 , Sep 3. PMID:24019758<ref>PMID:24019758</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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==See Also==
==See Also==
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*[[CREB-binding protein|CREB-binding protein]]
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*[[CREB-binding protein 3D structures|CREB-binding protein 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Histone acetyltransferase]]
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[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Mus musculus]]
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[[Category: Ghosh, G]]
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[[Category: Ghosh G]]
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[[Category: Mukherjee, S P]]
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[[Category: Mukherjee SP]]
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[[Category: Wright, P E]]
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[[Category: Wright PE]]
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[[Category: Nf-kappab]]
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[[Category: P65]]
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[[Category: Transcription]]
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Current revision

NMR structure of RelA-TAD/CBP-TAZ1 complex

PDB ID 2lww

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