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| | ==Solution NMR structures of BRD4 ET domain with JMJD6 peptide== | | ==Solution NMR structures of BRD4 ET domain with JMJD6 peptide== |
| - | <StructureSection load='6bnh' size='340' side='right' caption='[[6bnh]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='6bnh' size='340' side='right'caption='[[6bnh]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6bnh]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BNH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BNH FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6bnh]] 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=6BNH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6BNH FirstGlance]. <br> |
| - | </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=6bnh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bnh OCA], [http://pdbe.org/6bnh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bnh RCSB], [http://www.ebi.ac.uk/pdbsum/6bnh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bnh ProSAT]</span></td></tr> | + | </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=6bnh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bnh OCA], [https://pdbe.org/6bnh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6bnh RCSB], [https://www.ebi.ac.uk/pdbsum/6bnh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6bnh ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == 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> | + | [https://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 == | | == 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/JMJD6_HUMAN JMJD6_HUMAN]] Dioxygenase that can both act as a histone arginine demethylase and a lysyl-hydroxylase. Acts as a lysyl-hydroxylase that catalyzes 5-hydroxylation on specific lysine residues of target proteins such as U2AF2/U2AF65 and LUC7L2. Acts as a regulator of RNA splicing by mediating 5-hydroxylation of U2AF2/U2AF65, affecting the pre-mRNA splicing activity of U2AF2/U2AF65. In addition to peptidyl-lysine 5-dioxygenase activity, may act as a RNA hydroxylase, as suggested by its ability to bind single strand RNA. Also acts as an arginine demethylase which demethylates histone H3 at 'Arg-2' (H3R2me) and histone H4 at 'Arg-3' (H4R3me), thereby playing a role in histone code. However, histone arginine demethylation may not constitute the primary activity in vivo. Has no histone lysine demethylase activity. Required for differentiation of multiple organs during embryogenesis. Acts as a key regulator of hematopoietic differentiation: required for angiogenic sprouting by regulating the pre-mRNA splicing activity of U2AF2/U2AF65. Seems to be necessary for the regulation of macrophage cytokine responses.<ref>PMID:17947579</ref> <ref>PMID:19574390</ref> <ref>PMID:21060799</ref> <ref>PMID:20684070</ref> <ref>PMID:20679243</ref> | + | [https://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN] Plays a role in a process governing chromosomal dynamics during mitosis (By similarity). |
| | <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 6bnh" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6bnh" 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: Ju, Y]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Konuma, T]] | + | [[Category: Large Structures]] |
| - | [[Category: Ren, C]] | + | [[Category: Ju Y]] |
| - | [[Category: Sharma, R]] | + | [[Category: Konuma T]] |
| - | [[Category: Yu, D]] | + | [[Category: Ren C]] |
| - | [[Category: Zeng, L]] | + | [[Category: Sharma R]] |
| - | [[Category: Zhang, Q]] | + | [[Category: Yu D]] |
| - | [[Category: Zhao, C]] | + | [[Category: Zeng L]] |
| - | [[Category: Zhou, M M]] | + | [[Category: Zhang Q]] |
| - | [[Category: Bet]]
| + | [[Category: Zhao C]] |
| - | [[Category: Complex]]
| + | [[Category: Zhou M-M]] |
| - | [[Category: Rna]]
| + | |
| - | [[Category: Transcription-oxidoreductase complex]]
| + | |
| Structural highlights
Disease
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.[1] [2]
Function
BRD4_HUMAN Plays a role in a process governing chromosomal dynamics during mitosis (By similarity).
Publication Abstract from PubMed
Jumonji domain-containing protein 6 (JMJD6) is a member of the Jumonji C family of Fe(II) and 2-oxoglutarate (2OG) dependent oxygenases. It possesses unique bi-functional oxygenase activities, acting as both an arginine demethylase and a lysyl-hydroxylase. JMJD6 has been reported to be over-expressed in oral, breast, lung, and colon cancers and plays important roles in regulation of transcription through interactions with transcription regulator BRD4, histones, U2AF65, Luc7L3, and SRSF11. Here, we report a structural mechanism revealed by NMR of JMJD6 recognition by the extraterminal (ET) domain of BRD4 in that a JMJD6 peptide (Lys84-Asn96) adapts an alpha-helix when bound to the ET domain. This intermolecular recognition is established through JMJD6 interactions with the conserved hydrophobic core of the ET domain, and reinforced by electrostatic interactions of JMJD6 with residues in the inter-helical alpha1-alpha2 loop of the ET domain. Notably, this mode of ligand recognition is different from that of ET domain recognition of NSD3, LANA of herpesvirus, and integrase of MLV, which involves formation of an intermolecular amphipathic two- or three- strand antiparallel beta sheet. Furthermore, we demonstrate that the association between the BRD4 ET domain and JMJD6 likely requires a protein conformational change induced by single-stranded RNA binding.
Structural Mechanism of the Oxygenase JMJD6 Recognition by the Extraterminal (ET) Domain of BRD4.,Konuma T, Yu D, Zhao C, Ju Y, Sharma R, Ren C, Zhang Q, Zhou MM, Zeng L Sci Rep. 2017 Nov 24;7(1):16272. doi: 10.1038/s41598-017-16588-8. PMID:29176719[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ French CA, Miyoshi I, Kubonishi I, Grier HE, Perez-Atayde AR, Fletcher JA. BRD4-NUT fusion oncogene: a novel mechanism in aggressive carcinoma. Cancer Res. 2003 Jan 15;63(2):304-7. PMID:12543779
- ↑ French CA, Miyoshi I, Aster JC, Kubonishi I, Kroll TG, Dal Cin P, Vargas SO, Perez-Atayde AR, Fletcher JA. BRD4 bromodomain gene rearrangement in aggressive carcinoma with translocation t(15;19). Am J Pathol. 2001 Dec;159(6):1987-92. PMID:11733348 doi:10.1016/S0002-9440(10)63049-0
- ↑ Konuma T, Yu D, Zhao C, Ju Y, Sharma R, Ren C, Zhang Q, Zhou MM, Zeng L. Structural Mechanism of the Oxygenase JMJD6 Recognition by the Extraterminal (ET) Domain of BRD4. Sci Rep. 2017 Nov 24;7(1):16272. doi: 10.1038/s41598-017-16588-8. PMID:29176719 doi:http://dx.doi.org/10.1038/s41598-017-16588-8
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