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==Solution structure of the coiled-coil complex between MBD2 and p66alpha==
==Solution structure of the coiled-coil complex between MBD2 and p66alpha==
<StructureSection load='2l2l' size='340' side='right' caption='[[2l2l]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
<StructureSection load='2l2l' size='340' side='right'caption='[[2l2l]]' scene=''>
== Structural highlights ==
== Structural highlights ==
<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>
<table><tr><td colspan='2'>[[2l2l]] 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=2L2L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/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 HUMAN]), MBD2 ([http://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'>[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], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2l2l ProSAT]</span></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=2l2l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l2l OCA], [https://pdbe.org/2l2l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2l2l RCSB], [https://www.ebi.ac.uk/pdbsum/2l2l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2l2l ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== 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/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> 
[https://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>  
<div style="background-color:#fffaf0;">
== 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<ref>PMID:21490301</ref>
 
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==
==See Also==
*[[Methyl CpG binding protein|Methyl CpG binding protein]]
*[[Methyl CpG binding protein 3D structures|Methyl CpG binding protein 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Scarsdale, N]]
[[Category: Large Structures]]
[[Category: Williams, D C]]
[[Category: Scarsdale Jr N]]
[[Category: Coiled-coil]]
[[Category: Williams Jr DC]]
[[Category: Dna methylation]]
[[Category: Mbd2]]
[[Category: Nurd]]
[[Category: P66alpha]]
[[Category: Transferase]]

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