This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

2n3k

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 17:28, 15 August 2018

Human Brd4 ET domain in complex with MLV Integrase C-term

Structural highlights

2n3k is a 2 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	BRD4, HUNK1 (HUMAN)
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).

Publication Abstract from PubMed

The bromodomain and extraterminal domain (BET) protein family are promising therapeutic targets for a range of diseases linked to transcriptional activation, cancer, viral latency, and viral integration. Tandem bromodomains selectively tether BET proteins to chromatin by engaging cognate acetylated histone marks, and the extraterminal (ET) domain is the focal point for recruiting a range of cellular and viral proteins. BET proteins guide gamma-retroviral integration to transcription start sites and enhancers through bimodal interaction with chromatin and the gamma-retroviral integrase (IN). We report the NMR-derived solution structure of the Brd4 ET domain bound to a conserved peptide sequence from the C terminus of murine leukemia virus (MLV) IN. The complex reveals a protein-protein interaction governed by the binding-coupled folding of disordered regions in both interacting partners to form a well-structured intermolecular three-stranded beta sheet. In addition, we show that a peptide comprising the ET binding motif (EBM) of MLV IN can disrupt the cognate interaction of Brd4 with NSD3, and that substitutions of Brd4 ET residues essential for binding MLV IN also impair interaction of Brd4 with a number of cellular partners involved in transcriptional regulation and chromatin remodeling. This suggests that gamma-retroviruses have evolved the EBM to mimic a cognate interaction motif to achieve effective integration in host chromatin. Collectively, our findings identify key structural features of the ET domain of Brd4 that allow for interactions with both cellular and viral proteins.

Structure of the Brd4 ET domain bound to a C-terminal motif from gamma-retroviral integrases reveals a conserved mechanism of interaction.,Crowe BL, Larue RC, Yuan C, Hess S, Kvaratskhelia M, Foster MP Proc Natl Acad Sci U S A. 2016 Feb 23;113(8):2086-91. doi:, 10.1073/pnas.1516813113. Epub 2016 Feb 8. PMID:26858406^[3]

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
↑ Crowe BL, Larue RC, Yuan C, Hess S, Kvaratskhelia M, Foster MP. Structure of the Brd4 ET domain bound to a C-terminal motif from gamma-retroviral integrases reveals a conserved mechanism of interaction. Proc Natl Acad Sci U S A. 2016 Feb 23;113(8):2086-91. doi:, 10.1073/pnas.1516813113. Epub 2016 Feb 8. PMID:26858406 doi:http://dx.doi.org/10.1073/pnas.1516813113

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2n3k"

@@ Line 3: / Line 3: @@
 <StructureSection load='2n3k' size='340' side='right' caption='[[2n3k]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2n3k]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2N3K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2N3K FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2n3k]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2N3K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2N3K 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=2n3k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2n3k OCA], [http://pdbe.org/2n3k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2n3k RCSB], [http://www.ebi.ac.uk/pdbsum/2n3k PDBsum]</span></td></tr>
+</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=2n3k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2n3k OCA], [http://pdbe.org/2n3k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2n3k RCSB], [http://www.ebi.ac.uk/pdbsum/2n3k PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2n3k ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 23: / Line 24: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Crowe, B L]]
 [[Category: Foster, M P]]

2n3k

From Proteopedia

Revision as of 17:28, 15 August 2018

Human Brd4 ET domain in complex with MLV Integrase C-term

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox