2l2l

From Proteopedia

(Difference between revisions)

Revision as of 08:32, 10 November 2021

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, ProSAT

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 3: / Line 3: @@
 <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/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/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 [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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GATAD2A ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), MBD2 ([https://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://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>
 == 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>  [[https://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 ==

2l2l

From Proteopedia

Revision as of 08:32, 10 November 2021

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?)

Views

Personal tools

Navigation

Search

Toolbox