6g0p
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal Structure of the first bromodomain of human BRD4 in complex with an acetylated E2F1 peptide (K117ac/K120ac)== | |
| + | <StructureSection load='6g0p' size='340' side='right' caption='[[6g0p]], [[Resolution|resolution]] 1.30Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6g0p]] 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=6G0P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6G0P 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=6g0p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6g0p OCA], [http://pdbe.org/6g0p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6g0p RCSB], [http://www.ebi.ac.uk/pdbsum/6g0p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6g0p 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> | ||
| + | == 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/E2F1_HUMAN E2F1_HUMAN]] Transcription activator that binds DNA cooperatively with DP proteins through the E2 recognition site, 5'-TTTC[CG]CGC-3' found in the promoter region of a number of genes whose products are involved in cell cycle regulation or in DNA replication. The DRTF1/E2F complex functions in the control of cell-cycle progression from G1 to S phase. E2F1 binds preferentially RB1 in a cell-cycle dependent manner. It can mediate both cell proliferation and TP53/p53-dependent apoptosis.<ref>PMID:8170954</ref> <ref>PMID:10675335</ref> <ref>PMID:12717439</ref> <ref>PMID:17704056</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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 6g0p" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | == References == |
| - | [[Category: | + | <references/> |
| - | [[Category: | + | __TOC__ |
| + | </StructureSection> | ||
| + | [[Category: Human]] | ||
| + | [[Category: Arrowsmith, C H]] | ||
| + | [[Category: Bountra, C]] | ||
| + | [[Category: Delft, F von]] | ||
| + | [[Category: Edwards, A M]] | ||
[[Category: Filippakopoulos, P]] | [[Category: Filippakopoulos, P]] | ||
| - | [[Category: Edwards, A.M]] | ||
[[Category: Krojer, T]] | [[Category: Krojer, T]] | ||
| - | [[Category: | + | [[Category: Picaud, S]] |
| + | [[Category: Pike, A C.W]] | ||
[[Category: Sorrell, F]] | [[Category: Sorrell, F]] | ||
| + | [[Category: Bromodomain]] | ||
| + | [[Category: Complex]] | ||
| + | [[Category: Transcription]] | ||
Current revision
Crystal Structure of the first bromodomain of human BRD4 in complex with an acetylated E2F1 peptide (K117ac/K120ac)
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Categories: Human | Arrowsmith, C H | Bountra, C | Delft, F von | Edwards, A M | Filippakopoulos, P | Krojer, T | Picaud, S | Pike, A C.W | Sorrell, F | Bromodomain | Complex | Transcription
