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| | ==Solution NMR structure of Brd3 ET domain bound to Brg1 peptide== | | ==Solution NMR structure of Brd3 ET domain bound to Brg1 peptide== |
| - | <StructureSection load='6bgh' size='340' side='right'caption='[[6bgh]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='6bgh' size='340' side='right'caption='[[6bgh]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6bgh]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BGH OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6BGH FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6bgh]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BGH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6BGH FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BRD3, KIAA0043, RING3L ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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'>[http://proteopedia.org/fgij/fg.htm?mol=6bgh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bgh OCA], [http://pdbe.org/6bgh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bgh RCSB], [http://www.ebi.ac.uk/pdbsum/6bgh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bgh 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=6bgh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bgh OCA], [https://pdbe.org/6bgh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6bgh RCSB], [https://www.ebi.ac.uk/pdbsum/6bgh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6bgh ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/BRD3_HUMAN BRD3_HUMAN]] Note=A chromosomal aberration involving BRD3 is found in a rare, aggressive, and lethal carcinoma arising in midline organs of young people. Translocation t(15;9)(q14;q34) with NUT which produces a BRD3-NUT fusion protein. | + | [https://www.uniprot.org/uniprot/BRD3_HUMAN BRD3_HUMAN] Note=A chromosomal aberration involving BRD3 is found in a rare, aggressive, and lethal carcinoma arising in midline organs of young people. Translocation t(15;9)(q14;q34) with NUT which produces a BRD3-NUT fusion protein. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/BRD3_HUMAN BRD3_HUMAN]] Binds hyperacetylated chromatin and plays a role in the regulation of transcription, probably by chromatin remodeling and interaction with transcription factors. Regulates transcription by promoting the binding of the transcription factor GATA1 to its targets (By similarity). Regulates transcription of the CCND1 gene.<ref>PMID:18406326</ref> | + | [https://www.uniprot.org/uniprot/BRD3_HUMAN BRD3_HUMAN] Binds hyperacetylated chromatin and plays a role in the regulation of transcription, probably by chromatin remodeling and interaction with transcription factors. Regulates transcription by promoting the binding of the transcription factor GATA1 to its targets (By similarity). Regulates transcription of the CCND1 gene.<ref>PMID:18406326</ref> |
| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | Members of the bromodomain and extra-terminal domain (BET) family of proteins (bromodomain-containing (BRD) 2, 3, 4 and T) are widely expressed and highly conserved regulators of gene expression in eukaryotes. These proteins have been intimately linked to human disease and more than a dozen clinical trials are currently underway to test BET-protein inhibitors as modulators of cancer therapies. However, although it is clear that these proteins use their bromodomains to bind both histones and transcription factors bearing acetylated lysine residues, the molecular mechanisms by which BET-family proteins regulate gene expression are not well defined. In particular, the functions of the other domains such as the ET domain have been less extensively studied. Here, we examine the properties of the ET domain of BRD3 as a protein-protein interaction module. Using a combination of pulldown and biophysical assays, we demonstrate that BRD3 binds to a range of chromatin-remodeling complexes, including the NuRD, BAF and INO80 complexes, via a short linear 'KIKL' motif in one of the complex subunits. NMR-based structural analysis revealed that, surprisingly, this mode of interaction is shared by the AF9 and ENL transcriptional coregulators that contain an acetyllysine-binding YEATS domain and regulate transcriptional elongation. This observation establishes a functional commonality between these two families of cancer-related transcriptional regulators. In summary, our data provide insight into the mechanisms by which BET-family proteins might link chromatin acetylation to transcriptional outcomes and uncover an unexpected functional similarity between BET and YEATS family proteins.
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| - | The BRD3 ET domain recognizes a short peptide motif through a mechanism that is conserved across chromatin remodelers and transcriptional regulators.,Wai DC, Szyszka TN, Campbell AE, Kwong C, Wilkinson-White LE, Silva APG, Low JKK, Kwan AH, Gamsjaeger R, Chalmers JN, Patrick WM, Lu B, Vakoc CR, Blobel G, Mackay JP J Biol Chem. 2018 Mar 22. pii: RA117.000678. doi: 10.1074/jbc.RA117.000678. PMID:29567837<ref>PMID:29567837</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 6bgh" style="background-color:#fffaf0;"></div>
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| | ==See Also== | | ==See Also== |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Mackay, J P]] | + | [[Category: Mackay JP]] |
| - | [[Category: Szyszka, T N]] | + | [[Category: Szyszka TN]] |
| - | [[Category: Wai, D C]] | + | [[Category: Wai DC]] |
| - | [[Category: Transcription]]
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| - | [[Category: Transcription bromodomain bet protein]]
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