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6bnh

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Revision as of 08:50, 11 November 2020

Solution NMR structures of BRD4 ET domain with JMJD6 peptide

Structural highlights

6bnh is a 2 chain structure. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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). [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.^[3] ^[4] ^[5] ^[6] ^[7]

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^[8]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ Chang B, Chen Y, Zhao Y, Bruick RK. JMJD6 is a histone arginine demethylase. Science. 2007 Oct 19;318(5849):444-7. PMID:17947579 doi:318/5849/444
↑ Webby CJ, Wolf A, Gromak N, Dreger M, Kramer H, Kessler B, Nielsen ML, Schmitz C, Butler DS, Yates JR 3rd, Delahunty CM, Hahn P, Lengeling A, Mann M, Proudfoot NJ, Schofield CJ, Bottger A. Jmjd6 catalyses lysyl-hydroxylation of U2AF65, a protein associated with RNA splicing. Science. 2009 Jul 3;325(5936):90-3. PMID:19574390 doi:325/5936/90
↑ Hahn P, Wegener I, Burrells A, Bose J, Wolf A, Erck C, Butler D, Schofield CJ, Bottger A, Lengeling A. Analysis of Jmjd6 cellular localization and testing for its involvement in histone demethylation. PLoS One. 2010 Oct 29;5(10):e13769. doi: 10.1371/journal.pone.0013769. PMID:21060799 doi:10.1371/journal.pone.0013769
↑ Mantri M, Krojer T, Bagg EA, Webby CJ, Butler DS, Kochan G, Kavanagh KL, Oppermann U, McDonough MA, Schofield CJ. Crystal structure of the 2-oxoglutarate- and Fe(II)-dependent lysyl hydroxylase JMJD6. J Mol Biol. 2010 Aug 13;401(2):211-22. PMID:20684070
↑ Hong X, Zang J, White J, Wang C, Pan CH, Zhao R, Murphy RC, Dai S, Henson P, Kappler JW, Hagman J, Zhang G. Interaction of JMJD6 with single-stranded RNA. Proc Natl Acad Sci U S A. 2010 Aug 17;107(33):14568-72. Epub 2010 Aug 2. PMID:20679243 doi:10.1073/pnas.1008832107
↑ 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

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6bnh"

@@ Line 1: / Line 1: @@
 ==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]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
 == 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. 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://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'>[http://proteopedia.org/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>
 </table>
 == Disease ==
@@ Line 19: / Line 19: @@
 </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/>
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
 [[Category: Ju, Y]]
 [[Category: Konuma, T]]

6bnh

From Proteopedia

Revision as of 08:50, 11 November 2020

Solution NMR structures of BRD4 ET domain with JMJD6 peptide

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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