3p57: Difference between revisions

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-{{STRUCTURE_3p57|  PDB=3p57  |  SCENE=  }}
-===Crystal structure of the p300 TAZ2 domain bound to MEF2 on DNA===
-{{ABSTRACT_PUBMED_21278418}}
-==Disease==
+==Crystal structure of the p300 TAZ2 domain bound to MEF2 on DNA==
-[[http://www.uniprot.org/uniprot/EP300_HUMAN EP300_HUMAN]] Note=Defects in EP300 may play a role in epithelial cancer.  Note=Chromosomal aberrations involving EP300 may be a cause of acute myeloid leukemias. Translocation t(8;22)(p11;q13) with KAT6A.  Defects in EP300 are the cause of Rubinstein-Taybi syndrome type 2 (RSTS2) [MIM:[http://omim.org/entry/613684 613684]]. A disorder characterized by craniofacial abnormalities, postnatal growth deficiency, broad thumbs, broad big toes, mental retardation and a propensity for development of malignancies. Some individuals with RSTS2 have less severe mental impairment, more severe microcephaly, and a greater degree of changes in facial bone structure than RSTS1 patients.<ref>PMID:15706485</ref> [[http://www.uniprot.org/uniprot/MEF2A_HUMAN MEF2A_HUMAN]] Defects in MEF2A are a cause of coronary artery disease, autosomal dominant, type 1 (ADCAD1) [MIM:[http://omim.org/entry/608320 608320]]. A common heart disease characterized by reduced or absent blood flow in one or more of the arteries that encircle and supply the heart. Its most important complication is acute myocardial infarction.
+<StructureSection load='3p57' size='340' side='right'caption='[[3p57]], [[Resolution|resolution]] 2.19&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[3p57]] is a 13 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3P57 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3P57 FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1921&#8491;</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=3p57 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p57 OCA], [https://pdbe.org/3p57 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3p57 RCSB], [https://www.ebi.ac.uk/pdbsum/3p57 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3p57 ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/MEF2A_HUMAN MEF2A_HUMAN] Defects in MEF2A are a cause of coronary artery disease, autosomal dominant, type 1 (ADCAD1) [MIM:[https://omim.org/entry/608320 608320]. A common heart disease characterized by reduced or absent blood flow in one or more of the arteries that encircle and supply the heart. Its most important complication is acute myocardial infarction.
+== Function ==
+[https://www.uniprot.org/uniprot/MEF2A_HUMAN MEF2A_HUMAN] Transcriptional activator which binds specifically to the MEF2 element, 5'-YTA[AT](4)TAR-3', found in numerous muscle-specific genes. Also involved in the activation of numerous growth factor- and stress-induced genes. Mediates cellular functions not only in skeletal and cardiac muscle development, but also in neuronal differentiation and survival. Plays diverse roles in the control of cell growth, survival and apoptosis via p38 MAPK signaling in muscle-specific and/or growth factor-related transcription. In cerebellar granule neurons, phosphorylated and sumoylated MEF2A represses transcription of NUR77 promoting synaptic differentiation.<ref>PMID:9858528</ref> <ref>PMID:11904443</ref> <ref>PMID:12691662</ref> <ref>PMID:15834131</ref> <ref>PMID:16563226</ref> <ref>PMID:16371476</ref> <ref>PMID:16484498</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Transcription co-activators CBP and p300 are recruited by sequence-specific transcription factors to specific genomic loci to control gene expression. A highly conserved domain in CBP/p300, the TAZ2 domain, mediates direct interaction with a variety of transcription factors including the myocyte enhancer factor 2 (MEF2). Here we report the crystal structure of a ternary complex of the p300 TAZ2 domain bound to MEF2 on DNA at 2.2A resolution. The structure reveals three MEF2:DNA complexes binding to different sites of the TAZ2 domain. Using structure-guided mutations and a mammalian two-hybrid assay, we show that all three interfaces contribute to the binding of MEF2 to p300, suggesting that p300 may use one of the three interfaces to interact with MEF2 in different cellular contexts and that one p300 can bind three MEF2:DNA complexes simultaneously. These studies, together with previously characterized TAZ2 complexes bound to different transcription factors, demonstrate the potency and versatility of TAZ2 in protein-protein interactions. Our results also support a model wherein p300 promotes the assembly of a higher-order enhanceosome by simultaneous interactions with multiple DNA-bound transcription factors.
-==Function==
+Structure of p300 bound to MEF2 on DNA reveals a mechanism of enhanceosome assembly.,He J, Ye J, Cai Y, Riquelme C, Liu JO, Liu X, Han A, Chen L Nucleic Acids Res. 2011 May;39(10):4464-74. Epub 2011 Jan 29. PMID:21278418<ref>PMID:21278418</ref>
-[[http://www.uniprot.org/uniprot/EP300_HUMAN EP300_HUMAN]] Functions as histone acetyltransferase and regulates transcription via chromatin remodeling. Acetylates all four core histones in nucleosomes. Histone acetylation gives an epigenetic tag for transcriptional activation. Mediates cAMP-gene regulation by binding specifically to phosphorylated CREB protein. Also functions as acetyltransferase for nonhistone targets. Acetylates 'Lys-131' of ALX1 and acts as its coactivator in the presence of CREBBP. Acetylates SIRT2 and is proposed to indirectly increase the transcriptional activity of TP53 through acetylation and subsequent attenuation of SIRT2 deacetylase function. Acetylates HDAC1 leading to its inactivation and modulation of transcription. Acts as a TFAP2A-mediated transcriptional coactivator in presence of CITED2. Plays a role as a coactivator of NEUROD1-dependent transcription of the secretin and p21 genes and controls terminal differentiation of cells in the intestinal epithelium. Promotes cardiac myocyte enlargement. Can also mediate transcriptional repression. Binds to and may be involved in the transforming capacity of the adenovirus E1A protein. In case of HIV-1 infection, it is recruited by the viral protein Tat. Regulates Tat's transactivating activity and may help inducing chromatin remodeling of proviral genes. Acetylates FOXO1 and enhances its transcriptional activity.<ref>PMID:11701890</ref><ref>PMID:10733570</ref><ref>PMID:11430825</ref><ref>PMID:12586840</ref><ref>PMID:12929931</ref><ref>PMID:15186775</ref><ref>PMID:15890677</ref><ref>PMID:16762839</ref><ref>PMID:18722353</ref> [[http://www.uniprot.org/uniprot/MEF2A_HUMAN MEF2A_HUMAN]] Transcriptional activator which binds specifically to the MEF2 element, 5'-YTA[AT](4)TAR-3', found in numerous muscle-specific genes. Also involved in the activation of numerous growth factor- and stress-induced genes. Mediates cellular functions not only in skeletal and cardiac muscle development, but also in neuronal differentiation and survival. Plays diverse roles in the control of cell growth, survival and apoptosis via p38 MAPK signaling in muscle-specific and/or growth factor-related transcription. In cerebellar granule neurons, phosphorylated and sumoylated MEF2A represses transcription of NUR77 promoting synaptic differentiation.<ref>PMID:9858528</ref><ref>PMID:11904443</ref><ref>PMID:12691662</ref><ref>PMID:15834131</ref><ref>PMID:16563226</ref><ref>PMID:16371476</ref><ref>PMID:16484498</ref>
-==About this Structure==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[3p57]] is a 13 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3P57 OCA].
+</div>
+<div class="pdbe-citations 3p57" style="background-color:#fffaf0;"></div>
 ==See Also==
-*[[Histone acetyltransferase|Histone acetyltransferase]]
+*[[Histone acetyltransferase 3D structures|Histone acetyltransferase 3D structures]]
+*[[Myocyte enhancer factor 2|Myocyte enhancer factor 2]]
-==Reference==
+== References ==
-<ref group="xtra">PMID:021278418</ref><references group="xtra"/><references/>
+<references/>
-[[Category: Histone acetyltransferase]]
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: He, J.]]
+[[Category: Large Structures]]
-[[Category: Liu, J O.]]
+[[Category: Synthetic construct]]
-[[Category: Riquelme, C.]]
+[[Category: He J]]
-[[Category: Ye, J.]]
+[[Category: Liu JO]]
-[[Category: P300]]
+[[Category: Riquelme C]]
-[[Category: Protein-dna complex]]
+[[Category: Ye J]]
-[[Category: Transcription factor]]
-[[Category: Transcriptional activation]]
-[[Category: Transferase-transcription activator-dna complex]]
-[[Category: Zinc finger]]