View source for 6g0q


==Crystal Structure of the first bromodomain of human BRD4 in complex with an acetylated GATA1 peptide (K312ac/K315ac)==
<StructureSection load='6g0q' size='340' side='right' caption='[[6g0q]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6g0q]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6G0Q OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6G0Q FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></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>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BRD4, HUNK1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6g0q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6g0q OCA], [http://pdbe.org/6g0q PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6g0q RCSB], [http://www.ebi.ac.uk/pdbsum/6g0q PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6g0q ProSAT]</span></td></tr>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN]] Note=A chromosomal aberration involving BRD4 is found in a rare, aggressive, and lethal carcinoma arising in midline organs of young people. Translocation t(15;19)(q14;p13) with NUT which produces a BRD4-NUT fusion protein.<ref>PMID:12543779</ref> <ref>PMID:11733348</ref>  [[http://www.uniprot.org/uniprot/GATA1_HUMAN GATA1_HUMAN]] Beta-thalassemia-X-linked thrombocytopenia syndrome;Congenital erythropoietic porphyria;X-linked dyserythropoetic anemia with abnormal platelets and neutropenia;Thrombocytopenia with congenital dyserythropoietic anemia;Acute megakaryoblastic leukemia in Down syndrome;Transient myeloproliferative syndrome;Blackfan-Diamond anemia;Acute basophilic leukemia. The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry. 
== Function ==
[[http://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN]] Plays a role in a process governing chromosomal dynamics during mitosis (By similarity). [[http://www.uniprot.org/uniprot/GATA1_HUMAN GATA1_HUMAN]] Transcriptional activator or repressor which probably serves as a general switch factor for erythroid development. It binds to DNA sites with the consensus sequence 5'-[AT]GATA[AG]-3' within regulatory regions of globin genes and of other genes expressed in erythroid cells. Activates the transcription of genes involved in erythroid differentiation of K562 erythroleukemia cells, including HBB, HBG1/2, ALAS2 and HMBS (PubMed:24245781).<ref>PMID:22235304</ref> <ref>PMID:24245781</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Targeting bromodomains (BRDs) of the bromo-and-extra-terminal (BET) family offers opportunities for therapeutic intervention in cancer and other diseases. Here, we profile the interactomes of BRD2, BRD3, BRD4, and BRDT following treatment with the pan-BET BRD inhibitor JQ1, revealing broad rewiring of the interaction landscape, with three distinct classes of behavior for the 603 unique interactors identified. A group of proteins associate in a JQ1-sensitive manner with BET BRDs through canonical and new binding modes, while two classes of extra-terminal (ET)-domain binding motifs mediate acetylation-independent interactions. Last, we identify an unexpected increase in several interactions following JQ1 treatment that define negative functions for BRD3 in the regulation of rRNA synthesis and potentially RNAPII-dependent gene expression that result in decreased cell proliferation. Together, our data highlight the contributions of BET protein modules to their interactomes allowing for a better understanding of pharmacological rewiring in response to JQ1.

Interactome Rewiring Following Pharmacological Targeting of BET Bromodomains.,Lambert JP, Picaud S, Fujisawa T, Hou H, Savitsky P, Uuskula-Reimand L, Gupta GD, Abdouni H, Lin ZY, Tucholska M, Knight JDR, Gonzalez-Badillo B, St-Denis N, Newman JA, Stucki M, Pelletier L, Bandeira N, Wilson MD, Filippakopoulos P, Gingras AC Mol Cell. 2018 Dec 13. pii: S1097-2765(18)30948-1. doi:, 10.1016/j.molcel.2018.11.006. PMID:30554943<ref>PMID:30554943</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6g0q" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Arrowsmith, C H]]
[[Category: Bountra, C]]
[[Category: Delft, F von]]
[[Category: Edwards, A M]]
[[Category: Filippakopoulos, P]]
[[Category: Newman, J]]
[[Category: Picaud, S]]
[[Category: Sorrell, F]]
[[Category: Bromodomain]]
[[Category: Complex]]
[[Category: Transcription]]