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2kje
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==NMR structure of CBP TAZ2 and adenoviral E1A complex== | |
| + | <StructureSection load='2kje' size='340' side='right'caption='[[2kje]]' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[2kje]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Human_adenovirus_5 Human adenovirus 5]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KJE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KJE FirstGlance]. <br> | ||
| + | </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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</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=2kje FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kje OCA], [https://pdbe.org/2kje PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kje RCSB], [https://www.ebi.ac.uk/pdbsum/2kje PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kje ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/CBP_HUMAN CBP_HUMAN] Note=Chromosomal aberrations involving CREBBP may be a cause of acute myeloid leukemias. Translocation t(8;16)(p11;p13) with KAT6A; translocation t(11;16)(q23;p13.3) with MLL/HRX; translocation t(10;16)(q22;p13) with KAT6B. KAT6A-CREBBP may induce leukemia by inhibiting RUNX1-mediated transcription. Defects in CREBBP are a cause of Rubinstein-Taybi syndrome type 1 (RSTS1) [MIM:[https://omim.org/entry/180849 180849]. RSTS1 is an autosomal dominant disorder characterized by craniofacial abnormalities, broad thumbs, broad big toes, mental retardation and a propensity for development of malignancies.<ref>PMID:11331617</ref> <ref>PMID:12114483</ref> <ref>PMID:12566391</ref> <ref>PMID:15706485</ref> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/CBP_HUMAN CBP_HUMAN] 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.<ref>PMID:9707565</ref> <ref>PMID:11154691</ref> <ref>PMID:12738767</ref> <ref>PMID:12929931</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/kj/2kje_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=2kje ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The adenovirus early region 1A (E1A) oncoprotein mediates cell transformation by deregulating host cellular processes and activating viral gene expression by recruitment of cellular proteins that include cyclic-AMP response element binding (CREB) binding protein (CBP)/p300 and the retinoblastoma protein (pRb). While E1A is capable of independent interaction with CBP/p300 or pRb, simultaneous binding of both proteins is required for maximal biological activity. To obtain insights into the mechanism by which E1A hijacks the cellular transcription machinery by competing with essential transcription factors for binding to CBP/p300, we have determined the structure of the complex between the transcriptional adaptor zinc finger-2 (TAZ2) domain of CBP and the conserved region-1 (CR1) domain of E1A. The E1A CR1 domain is unstructured in the free state and upon binding folds into a local helical structure mediated by an extensive network of intermolecular hydrophobic contacts. By NMR titrations, we show that E1A efficiently competes with the N-terminal transactivation domain of p53 for binding to TAZ2 and that pRb interacts with E1A at 2 independent sites located in CR1 and CR2. We show that pRb and the CBP TAZ2 domain can bind simultaneously to the CR1 site of E1A to form a ternary complex and propose a structural model for the pRb:E1A:CBP complex on the basis of published x-ray data for homologous binary complexes. These observations reveal the molecular basis by which E1A inhibits p53-mediated transcriptional activation and provide a rationale for the efficiency of cellular transformation by the adenoviral E1A oncoprotein. | ||
| - | + | Structural basis for subversion of cellular control mechanisms by the adenoviral E1A oncoprotein.,Ferreon JC, Martinez-Yamout MA, Dyson HJ, Wright PE Proc Natl Acad Sci U S A. 2009 Aug 11;106(32):13260-5. Epub 2009 Jul 27. PMID:19651603<ref>PMID:19651603</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| + | </div> | ||
| + | <div class="pdbe-citations 2kje" style="background-color:#fffaf0;"></div> | ||
| - | + | ==See Also== | |
| + | *[[CREB-binding protein 3D structures|CREB-binding protein 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Human adenovirus 5]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Dyson H]] | ||
| + | [[Category: Ferreon JC]] | ||
| + | [[Category: Martinez-Yamout M]] | ||
| + | [[Category: Wright PE]] | ||
Current revision
NMR structure of CBP TAZ2 and adenoviral E1A complex
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