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| | ==Crystal structure of bromodomain 1 of mouse Brd4 in complex with histone H3-K(ac)14== | | ==Crystal structure of bromodomain 1 of mouse Brd4 in complex with histone H3-K(ac)14== |
| - | <StructureSection load='3jvk' size='340' side='right' caption='[[3jvk]], [[Resolution|resolution]] 1.80Å' scene=''> | + | <StructureSection load='3jvk' size='340' side='right'caption='[[3jvk]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3jvk]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3JVK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3JVK FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3jvk]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3JVK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3JVK 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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8Å</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='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=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3jvj|3jvj]], [[3jvl|3jvl]], [[3jvm|3jvm]]</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=3jvk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3jvk OCA], [https://pdbe.org/3jvk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3jvk RCSB], [https://www.ebi.ac.uk/pdbsum/3jvk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3jvk ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Brd4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=3jvk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3jvk OCA], [http://pdbe.org/3jvk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3jvk RCSB], [http://www.ebi.ac.uk/pdbsum/3jvk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3jvk ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/BRD4_MOUSE BRD4_MOUSE]] Plays a role in a process governing chromosomal dynamics during mitosis.<ref>PMID:10938129</ref> | + | [https://www.uniprot.org/uniprot/BRD4_MOUSE BRD4_MOUSE] Plays a role in a process governing chromosomal dynamics during mitosis.<ref>PMID:10938129</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | ==See Also== | | ==See Also== |
| - | *[[Bromodomain-containing protein|Bromodomain-containing protein]] | + | *[[Bromodomain-containing protein 3D structures|Bromodomain-containing protein 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Blankenfeldt, W]] | + | [[Category: Large Structures]] |
| - | [[Category: Geyer, M]] | + | [[Category: Mus musculus]] |
| - | [[Category: Vollmuth, F]] | + | [[Category: Blankenfeldt W]] |
| - | [[Category: Alpha helical]] | + | [[Category: Geyer M]] |
| - | [[Category: Bromodomain]] | + | [[Category: Vollmuth F]] |
| - | [[Category: N-acetyl lysine recognition]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
Function
BRD4_MOUSE Plays a role in a process governing chromosomal dynamics during mitosis.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Brd4 is a member of the bromodomains and extra terminal domain (BET) family of proteins that recognize acetylated chromatin structures through their bromodomains and act as transcriptional activators. Brd4 functions as an associated factor and positive regulator of P-TEFb, a Cdk9-cyclin T heterodimer that stimulates transcriptional elongation by RNA polymerase II. Here, the crystal structures of the two bromodomains of Brd4 (BD1 and BD2) were determined at 1.5 and 1.2 A resolution, respectively. Complex formation of BD1 with a histone H3 tail polypeptide encompassing residues 12-19 showed binding of the Nzeta-acetylated lysine 14 to the conserved asparagine 140 of Brd4. In contrast, in BD2 the N-terminal linker sequence was found to interact with the binding site for acetylated lysines of the adjacent molecule to form continuous strings in the crystal lattice. This assembly shows for the first time a different binding ligand than acetylated lysine indicating that also other sequence compositions may be able to form similar interaction networks. Isothermal titration calorimetry revealed best binding of BD1 to H3 and of BD2 to H4 acetylated lysine sequences, suggesting alternating histone recognition specificities. Intriguingly, an acetylated lysine motif from cyclin T1 bound similarly well to BD2. Whereas the structure of Brd2 BD1 suggested its dimer formation, both Brd4 bromodomains appeared monomeric in solution as shown by size exclusion chromatography and mutational analyses.
Structures of the dual bromodomains of the P-TEFb-activating protein Brd4 at atomic resolution.,Vollmuth F, Blankenfeldt W, Geyer M J Biol Chem. 2009 Dec 25;284(52):36547-56. Epub 2009 Oct 13. PMID:19828451[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Dey A, Ellenberg J, Farina A, Coleman AE, Maruyama T, Sciortino S, Lippincott-Schwartz J, Ozato K. A bromodomain protein, MCAP, associates with mitotic chromosomes and affects G(2)-to-M transition. Mol Cell Biol. 2000 Sep;20(17):6537-49. PMID:10938129
- ↑ Vollmuth F, Blankenfeldt W, Geyer M. Structures of the dual bromodomains of the P-TEFb-activating protein Brd4 at atomic resolution. J Biol Chem. 2009 Dec 25;284(52):36547-56. Epub 2009 Oct 13. PMID:19828451 doi:10.1074/jbc.M109.033712
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