2i7k

From Proteopedia

(Difference between revisions)

Current revision

Solution Structure of the Bromodomain of Human BRD7 Protein

Structural highlights

2i7k is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

BRD7_HUMAN Acts both as coactivator and as corepressor. May play a role in chromatin remodeling. Activator of the Wnt signaling pathway in a DVL1-dependent manner by negatively regulating the GSK3B phosphotransferase activity. Induces dephosphorylation of GSK3B at 'Tyr-216'. Down-regulates TRIM24-mediated activation of transcriptional activation by AR (By similarity). Transcriptional corepressor that down-regulates the expression of target genes. Binds to target promoters, leading to increased histone H3 acetylation at 'Lys-9' (H3K9ac). Binds to the ESR1 promoter. Recruits BRCA1 and POU2F1 to the ESR1 promoter. Coactivator for TP53-mediated activation of transcription of a set of target genes. Required for TP53-mediated cell-cycle arrest in response to oncogene activation. Promotes acetylation of TP53 at 'Lys-382', and thereby promotes efficient recruitment of TP53 to target promoters. Inhibits cell cycle progression from G1 to S phase.^[1] ^[2] ^[3] ^[4] ^[5]

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

BRD7 is an important protein tightly associated with Nasopharyngeal carcinoma (NPC). Overexpression of BRD7 inhibits NPC cell growth and cell cycle by transcriptionally regulating the cell cycle related genes. BRD7 contains a bromodomain that is found in many chromatin-associated proteins and in nearly all known nuclear histone acetyltransferases (HATs) and plays an important role in chromatin remodeling and transcriptional activation. Here, we report the solution structure of BRD7 bromodomain determined by NMR spectroscopy, and its binding specificity revealed by NMR titration with several acetylated histone peptides. We find that BRD7 bromodomain contains the typical left-handed four-helix bundle topology, and can bind with weak affinity to lysine-acetylated peptides derived from histone H3 with K9 or K14 acetylated and from histone H4 with K8, K12 or K16 acetylated. Our results show that BRD7 bromodomain lacks inherent binding specificity when binding to histones in vitro.

Solution structure of BRD7 bromodomain and its interaction with acetylated peptides from histone H3 and H4.,Sun H, Liu J, Zhang J, Shen W, Huang H, Xu C, Dai H, Wu J, Shi Y Biochem Biophys Res Commun. 2007 Jun 29;358(2):435-41. Epub 2007 May 2. PMID:17498659^[6]

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

References

↑ Peng C, Zhou J, Liu HY, Zhou M, Wang LL, Zhang QH, Yang YX, Xiong W, Shen SR, Li XL, Li GY. The transcriptional regulation role of BRD7 by binding to acetylated histone through bromodomain. J Cell Biochem. 2006 Mar 1;97(4):882-92. PMID:16265664 doi:http://dx.doi.org/10.1002/jcb.20645
↑ Zhou M, Liu H, Xu X, Zhou H, Li X, Peng C, Shen S, Xiong W, Ma J, Zeng Z, Fang S, Nie X, Yang Y, Zhou J, Xiang J, Cao L, Peng S, Li S, Li G. Identification of nuclear localization signal that governs nuclear import of BRD7 and its essential roles in inhibiting cell cycle progression. J Cell Biochem. 2006 Jul 1;98(4):920-30. PMID:16475162 doi:http://dx.doi.org/10.1002/jcb.20788
↑ Harte MT, O'Brien GJ, Ryan NM, Gorski JJ, Savage KI, Crawford NT, Mullan PB, Harkin DP. BRD7, a subunit of SWI/SNF complexes, binds directly to BRCA1 and regulates BRCA1-dependent transcription. Cancer Res. 2010 Mar 15;70(6):2538-47. doi: 10.1158/0008-5472.CAN-09-2089. Epub, 2010 Mar 9. PMID:20215511 doi:http://dx.doi.org/10.1158/0008-5472.CAN-09-2089
↑ Drost J, Mantovani F, Tocco F, Elkon R, Comel A, Holstege H, Kerkhoven R, Jonkers J, Voorhoeve PM, Agami R, Del Sal G. BRD7 is a candidate tumour suppressor gene required for p53 function. Nat Cell Biol. 2010 Apr;12(4):380-9. doi: 10.1038/ncb2038. Epub 2010 Mar 14. PMID:20228809 doi:http://dx.doi.org/10.1038/ncb2038
↑ Burrows AE, Smogorzewska A, Elledge SJ. Polybromo-associated BRG1-associated factor components BRD7 and BAF180 are critical regulators of p53 required for induction of replicative senescence. Proc Natl Acad Sci U S A. 2010 Aug 10;107(32):14280-5. doi:, 10.1073/pnas.1009559107. Epub 2010 Jul 26. PMID:20660729 doi:http://dx.doi.org/10.1073/pnas.1009559107
↑ Sun H, Liu J, Zhang J, Shen W, Huang H, Xu C, Dai H, Wu J, Shi Y. Solution structure of BRD7 bromodomain and its interaction with acetylated peptides from histone H3 and H4. Biochem Biophys Res Commun. 2007 Jun 29;358(2):435-41. Epub 2007 May 2. PMID:17498659 doi:http://dx.doi.org/10.1016/j.bbrc.2007.04.139

1 Structural highlights
2 Function
3 Evolutionary Conservation
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/2i7k"

@@ Line 1: / Line 1: @@
 ==Solution Structure of the Bromodomain of Human BRD7 Protein==
-<StructureSection load='2i7k' size='340' side='right'caption='[[2i7k]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
+<StructureSection load='2i7k' size='340' side='right'caption='[[2i7k]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2i7k]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2I7K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2I7K FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2i7k]] is a 1 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=2I7K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2I7K FirstGlance]. <br>
-</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BRD7 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=2i7k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2i7k OCA], [https://pdbe.org/2i7k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2i7k RCSB], [https://www.ebi.ac.uk/pdbsum/2i7k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2i7k ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/BRD7_HUMAN BRD7_HUMAN]] Acts both as coactivator and as corepressor. May play a role in chromatin remodeling. Activator of the Wnt signaling pathway in a DVL1-dependent manner by negatively regulating the GSK3B phosphotransferase activity. Induces dephosphorylation of GSK3B at 'Tyr-216'. Down-regulates TRIM24-mediated activation of transcriptional activation by AR (By similarity). Transcriptional corepressor that down-regulates the expression of target genes. Binds to target promoters, leading to increased histone H3 acetylation at 'Lys-9' (H3K9ac). Binds to the ESR1 promoter. Recruits BRCA1 and POU2F1 to the ESR1 promoter. Coactivator for TP53-mediated activation of transcription of a set of target genes. Required for TP53-mediated cell-cycle arrest in response to oncogene activation. Promotes acetylation of TP53 at 'Lys-382', and thereby promotes efficient recruitment of TP53 to target promoters. Inhibits cell cycle progression from G1 to S phase.<ref>PMID:16265664</ref> <ref>PMID:16475162</ref> <ref>PMID:20215511</ref> <ref>PMID:20228809</ref> <ref>PMID:20660729</ref>
+[https://www.uniprot.org/uniprot/BRD7_HUMAN BRD7_HUMAN] Acts both as coactivator and as corepressor. May play a role in chromatin remodeling. Activator of the Wnt signaling pathway in a DVL1-dependent manner by negatively regulating the GSK3B phosphotransferase activity. Induces dephosphorylation of GSK3B at 'Tyr-216'. Down-regulates TRIM24-mediated activation of transcriptional activation by AR (By similarity). Transcriptional corepressor that down-regulates the expression of target genes. Binds to target promoters, leading to increased histone H3 acetylation at 'Lys-9' (H3K9ac). Binds to the ESR1 promoter. Recruits BRCA1 and POU2F1 to the ESR1 promoter. Coactivator for TP53-mediated activation of transcription of a set of target genes. Required for TP53-mediated cell-cycle arrest in response to oncogene activation. Promotes acetylation of TP53 at 'Lys-382', and thereby promotes efficient recruitment of TP53 to target promoters. Inhibits cell cycle progression from G1 to S phase.<ref>PMID:16265664</ref> <ref>PMID:16475162</ref> <ref>PMID:20215511</ref> <ref>PMID:20228809</ref> <ref>PMID:20660729</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 32: / Line 32: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Huang, H]]
+[[Category: Huang H]]
-[[Category: Liu, J]]
+[[Category: Liu J]]
-[[Category: Shi, Y]]
+[[Category: Shi Y]]
-[[Category: Sun, H]]
+[[Category: Sun H]]
-[[Category: Wu, J]]
+[[Category: Wu J]]
-[[Category: Zhang, J]]
+[[Category: Zhang J]]
-[[Category: Helix]]
-[[Category: Left-handed four-helix bundle]]
-[[Category: Transcription]]

2i7k

From Proteopedia

Current revision

Solution Structure of the Bromodomain of Human BRD7 Protein

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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