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| | ==Complex between BD1 of Brd3 and GATA-1 C-tail== | | ==Complex between BD1 of Brd3 and GATA-1 C-tail== |
| - | <StructureSection load='2l5e' size='340' side='right' caption='[[2l5e]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2l5e' size='340' side='right'caption='[[2l5e]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2l5e]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2L5E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2L5E FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2l5e]] 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=2L5E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2L5E FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ALY:N(6)-ACETYLLYSINE'>ALY</scene></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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Brd3, mCG_11349, RP23-328F3.1-001 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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></td></tr> |
| - | <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=2l5e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l5e OCA], [http://pdbe.org/2l5e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2l5e RCSB], [http://www.ebi.ac.uk/pdbsum/2l5e PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2l5e 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=2l5e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l5e OCA], [https://pdbe.org/2l5e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2l5e RCSB], [https://www.ebi.ac.uk/pdbsum/2l5e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2l5e ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/BRD3_MOUSE BRD3_MOUSE] Chromatin reader that recognizes and binds hyperacetylated chromatin and plays a role in the regulation of transcription, probably by chromatin remodeling and interaction with transcription factors (PubMed:21536911). Regulates transcription by promoting the binding of the transcription factor GATA1 to its targets (PubMed:21536911).<ref>PMID:21536911</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 2l5e" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 2l5e" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Bromodomain-containing protein 3D structures|Bromodomain-containing protein 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Blobel, G A]] | + | [[Category: Mus musculus]] |
| - | [[Category: Gamsjaeger, R]] | + | [[Category: Blobel GA]] |
| - | [[Category: Lamonica, J M]] | + | [[Category: Gamsjaeger R]] |
| - | [[Category: Mackay, J P]]
| + | [[Category: Lamonica JM]] |
| - | [[Category: Webb, S R]]
| + | [[Category: Mackay JP]] |
| - | [[Category: Brd3]] | + | [[Category: Webb SR]] |
| - | [[Category: Gata-1]] | + | |
| - | [[Category: Histone code]] | + | |
| - | [[Category: Nuclear protein-transcription complex]]
| + | |
| Structural highlights
Function
BRD3_MOUSE Chromatin reader that recognizes and binds hyperacetylated chromatin and plays a role in the regulation of transcription, probably by chromatin remodeling and interaction with transcription factors (PubMed:21536911). Regulates transcription by promoting the binding of the transcription factor GATA1 to its targets (PubMed:21536911).[1]
Publication Abstract from PubMed
Recent data demonstrate that small synthetic compounds specifically targeting bromodomain proteins can modulate the expression of cancer-related or inflammatory genes. Although these studies have focused on the ability of bromodomains to recognize acetylated histones, it is increasingly becoming clear that histone-like modifications exist on other important proteins, such as transcription factors. However, our understanding of the molecular mechanisms through which these modifications modulate protein function is far from complete. The transcription factor GATA1 can be acetylated at lysine residues adjacent to the zinc finger domains, and this acetylation is essential for the normal chromatin occupancy of GATA1. We have recently identified the bromodomain-containing protein Brd3 as a cofactor that interacts with acetylated GATA1 and shown that this interaction is essential for the targeting of GATA1 to chromatin. Here we describe the structural basis for this interaction. Our data reveal for the first time the molecular details of an interaction between a transcription factor bearing multiple acetylation modifications and its cognate recognition module. We also show that this interaction can be inhibited by an acetyllysine mimic, highlighting the importance of further increasing the specificity of compounds that target bromodomain and extraterminal (BET) bromodomains in order to fully realize their therapeutic potential.
Structural basis and specificity of acetylated transcription factor GATA1 recognition by BET family bromodomain protein Brd3.,Gamsjaeger R, Webb SR, Lamonica JM, Billin A, Blobel GA, Mackay JP Mol Cell Biol. 2011 Jul;31(13):2632-40. doi: 10.1128/MCB.05413-11. Epub 2011 May , 9. PMID:21555453[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Lamonica JM, Deng W, Kadauke S, Campbell AE, Gamsjaeger R, Wang H, Cheng Y, Billin AN, Hardison RC, Mackay JP, Blobel GA. Bromodomain protein Brd3 associates with acetylated GATA1 to promote its chromatin occupancy at erythroid target genes. Proc Natl Acad Sci U S A. 2011 May 31;108(22):E159-68. PMID:21536911 doi:10.1073/pnas.1102140108
- ↑ Gamsjaeger R, Webb SR, Lamonica JM, Billin A, Blobel GA, Mackay JP. Structural basis and specificity of acetylated transcription factor GATA1 recognition by BET family bromodomain protein Brd3. Mol Cell Biol. 2011 Jul;31(13):2632-40. doi: 10.1128/MCB.05413-11. Epub 2011 May , 9. PMID:21555453 doi:http://dx.doi.org/10.1128/MCB.05413-11
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