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2l2l

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Revision as of 11:54, 11 September 2015

Solution structure of the coiled-coil complex between MBD2 and p66alpha

Structural highlights

2l2l 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:	GATAD2A (HUMAN), MBD2 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Function

[P66A_HUMAN] Transcriptional repressor. Enhances MBD2-mediated repression. Efficient repression requires the presence of GATAD2B.^[1] ^[2] [MBD2_HUMAN] Binds CpG islands in promoters where the DNA is methylated at position 5 of cytosine within CpG dinucleotides. Binds hemimethylated DNA as well. Recruits histone deacetylases and DNA methyltransferases. Acts as transcriptional repressor and plays a role in gene silencing. Functions as a scaffold protein, targeting GATAD2A and GATAD2B to chromatin to promote repression. May enhance the activation of some unmethylated cAMP-responsive promoters.^[3] ^[4] ^[5] ^[6] ^[7] ^[8]

Publication Abstract from PubMed

Nucleosome remodeling complexes comprise several large families of chromatin modifiers that integrate multiple epigenetic control signals to play key roles in cell type-specific transcription regulation. We previously isolated a methyl-binding domain protein 2 (MBD2)-containing nucleosome remodeling and deacetylation (NuRD) complex from primary erythroid cells and showed that MBD2 contributes to DNA methylation-dependent embryonic and fetal beta-type globin gene silencing during development in vivo. Here we present structural and biophysical details of the coiled-coil interaction between MBD2 and p66alpha, a critical component of the MBD2-NuRD complex. We show that enforced expression of the isolated p66alpha coiled-coil domain relieves MBD2-mediated globin gene silencing and that the expressed peptide interacts only with a subset of components of the MBD2-NuRD complex that does not include native p66alpha or Mi-2. These results demonstrate the central importance of the coiled-coil interaction and suggest that MBD2-dependent DNA methylation-driven gene silencing can be disrupted by selectively targeting this coiled-coil complex.

p66{alpha}-MBD2 coiled-coil interaction and recruitment of Mi-2 are critical for globin gene silencing by the MBD2-NuRD complex.,Gnanapragasam MN, Scarsdale JN, Amaya ML, Webb HD, Desai MA, Walavalkar NM, Wang SZ, Zhu SZ, Ginder GD, Williams DC Jr Proc Natl Acad Sci U S A. 2011 Apr 13. PMID:21490301^[9]

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

References

↑ Brackertz M, Boeke J, Zhang R, Renkawitz R. Two highly related p66 proteins comprise a new family of potent transcriptional repressors interacting with MBD2 and MBD3. J Biol Chem. 2002 Oct 25;277(43):40958-66. Epub 2002 Aug 14. PMID:12183469 doi:http://dx.doi.org/10.1074/jbc.M207467200
↑ Brackertz M, Gong Z, Leers J, Renkawitz R. p66alpha and p66beta of the Mi-2/NuRD complex mediate MBD2 and histone interaction. Nucleic Acids Res. 2006 Jan 13;34(2):397-406. Print 2006. PMID:16415179 doi:http://dx.doi.org/10.1093/nar/gkj437
↑ Ng HH, Zhang Y, Hendrich B, Johnson CA, Turner BM, Erdjument-Bromage H, Tempst P, Reinberg D, Bird A. MBD2 is a transcriptional repressor belonging to the MeCP1 histone deacetylase complex. Nat Genet. 1999 Sep;23(1):58-61. PMID:10471499 doi:http://dx.doi.org/10.1038/12659
↑ Tatematsu KI, Yamazaki T, Ishikawa F. MBD2-MBD3 complex binds to hemi-methylated DNA and forms a complex containing DNMT1 at the replication foci in late S phase. Genes Cells. 2000 Aug;5(8):677-88. PMID:10947852
↑ Fujita H, Fujii R, Aratani S, Amano T, Fukamizu A, Nakajima T. Antithetic effects of MBD2a on gene regulation. Mol Cell Biol. 2003 Apr;23(8):2645-57. PMID:12665568
↑ Brackertz M, Gong Z, Leers J, Renkawitz R. p66alpha and p66beta of the Mi-2/NuRD complex mediate MBD2 and histone interaction. Nucleic Acids Res. 2006 Jan 13;34(2):397-406. Print 2006. PMID:16415179 doi:http://dx.doi.org/10.1093/nar/gkj437
↑ Cramer JM, Scarsdale JN, Walavalkar NM, Buchwald WA, Ginder GD, Williams DC Jr. Probing the Dynamic Distribution of Bound States for Methyl-cytosine Binding Domains on DNA. J Biol Chem. 2013 Dec 4. PMID:24307175 doi:http://dx.doi.org/10.1074/jbc.M113.512236
↑ Hendrich B, Bird A. Identification and characterization of a family of mammalian methyl-CpG binding proteins. Mol Cell Biol. 1998 Nov;18(11):6538-47. PMID:9774669
↑ Gnanapragasam MN, Scarsdale JN, Amaya ML, Webb HD, Desai MA, Walavalkar NM, Wang SZ, Zhu SZ, Ginder GD, Williams DC Jr. p66{alpha}-MBD2 coiled-coil interaction and recruitment of Mi-2 are critical for globin gene silencing by the MBD2-NuRD complex. Proc Natl Acad Sci U S A. 2011 Apr 13. PMID:21490301 doi:10.1073/pnas.1015341108

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2l2l"

@@ Line 2: / Line 2: @@
 <StructureSection load='2l2l' size='340' side='right' caption='[[2l2l]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2l2l]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2L2L OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2L2L FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2l2l]] 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=2L2L OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2L2L FirstGlance]. <br>
-</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GATAD2A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), MBD2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GATAD2A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), MBD2 ([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=2l2l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l2l OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2l2l RCSB], [http://www.ebi.ac.uk/pdbsum/2l2l PDBsum]</span></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=2l2l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l2l OCA], [http://pdbe.org/2l2l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2l2l RCSB], [http://www.ebi.ac.uk/pdbsum/2l2l PDBsum]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/P66A_HUMAN P66A_HUMAN]] Transcriptional repressor. Enhances MBD2-mediated repression. Efficient repression requires the presence of GATAD2B.<ref>PMID:12183469</ref> <ref>PMID:16415179</ref>
+[[http://www.uniprot.org/uniprot/P66A_HUMAN P66A_HUMAN]] Transcriptional repressor. Enhances MBD2-mediated repression. Efficient repression requires the presence of GATAD2B.<ref>PMID:12183469</ref> <ref>PMID:16415179</ref>  [[http://www.uniprot.org/uniprot/MBD2_HUMAN MBD2_HUMAN]] Binds CpG islands in promoters where the DNA is methylated at position 5 of cytosine within CpG dinucleotides. Binds hemimethylated DNA as well. Recruits histone deacetylases and DNA methyltransferases. Acts as transcriptional repressor and plays a role in gene silencing. Functions as a scaffold protein, targeting GATAD2A and GATAD2B to chromatin to promote repression. May enhance the activation of some unmethylated cAMP-responsive promoters.<ref>PMID:10471499</ref> <ref>PMID:10947852</ref> <ref>PMID:12665568</ref> <ref>PMID:16415179</ref> <ref>PMID:24307175</ref> <ref>PMID:9774669</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 16: / Line 16: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2l2l" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 23: / Line 24: @@
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Scarsdale, N]]
 [[Category: Williams, D C]]

2l2l

From Proteopedia

Revision as of 11:54, 11 September 2015

Solution structure of the coiled-coil complex between MBD2 and p66alpha

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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