6gyt
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 6gyt is ON HOLD Authors: Panne, D., Ortega, E. Description: Transcription factor dimerization activates the p300 acetyltransferase [[Category: Unre...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Transcription factor dimerization activates the p300 acetyltransferase== | |
| + | <StructureSection load='6gyt' size='340' side='right'caption='[[6gyt]], [[Resolution|resolution]] 2.50Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6gyt]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Xenopus_laevis Xenopus laevis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GYT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6GYT 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]] 2.5Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ALY:N(6)-ACETYLLYSINE'>ALY</scene>, <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=6gyt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gyt OCA], [https://pdbe.org/6gyt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6gyt RCSB], [https://www.ebi.ac.uk/pdbsum/6gyt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6gyt ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [https://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:[https://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> | ||
| + | == Function == | ||
| + | [https://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> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The transcriptional co-activator p300 is a histone acetyltransferase (HAT) that is typically recruited to transcriptional enhancers and regulates gene expression by acetylating chromatin. Here we show that the activation of p300 directly depends on the activation and oligomerization status of transcription factor ligands. Using two model transcription factors, IRF3 and STAT1, we demonstrate that transcription factor dimerization enables the trans-autoacetylation of p300 in a highly conserved and intrinsically disordered autoinhibitory lysine-rich loop, resulting in p300 activation. We describe a crystal structure of p300 in which the autoinhibitory loop invades the active site of a neighbouring HAT domain, revealing a snapshot of a trans-autoacetylation reaction intermediate. Substrate access to the active site involves the rearrangement of an autoinhibitory RING domain. Our data explain how cellular signalling and the activation and dimerization of transcription factors control the activation of p300, and therefore explain why gene transcription is associated with chromatin acetylation. | ||
| - | + | Transcription factor dimerization activates the p300 acetyltransferase.,Ortega E, Rengachari S, Ibrahim Z, Hoghoughi N, Gaucher J, Holehouse AS, Khochbin S, Panne D Nature. 2018 Oct;562(7728):538-544. doi: 10.1038/s41586-018-0621-1. Epub 2018 Oct, 15. PMID:30323286<ref>PMID:30323286</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 6gyt" style="background-color:#fffaf0;"></div> |
| - | [[Category: Ortega | + | |
| + | ==See Also== | ||
| + | *[[Histone acetyltransferase 3D structures|Histone acetyltransferase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Xenopus laevis]] | ||
| + | [[Category: Ortega E]] | ||
| + | [[Category: Panne D]] | ||
Current revision
Transcription factor dimerization activates the p300 acetyltransferase
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