6c1a: Difference between revisions

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==MBD2 in complex with methylated DNA==
==MBD2 in complex with methylated DNA==
<StructureSection load='6c1a' size='340' side='right' caption='[[6c1a]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
<StructureSection load='6c1a' size='340' side='right'caption='[[6c1a]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[6c1a]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6C1A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6C1A FirstGlance]. <br>
<table><tr><td colspan='2'>[[6c1a]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6C1A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6C1A FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.05&#8491;</td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=5CM:5-METHYL-2-DEOXY-CYTIDINE-5-MONOPHOSPHATE'>5CM</scene></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5CM:5-METHYL-2-DEOXY-CYTIDINE-5-MONOPHOSPHATE'>5CM</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">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'>[https://proteopedia.org/fgij/fg.htm?mol=6c1a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6c1a OCA], [https://pdbe.org/6c1a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6c1a RCSB], [https://www.ebi.ac.uk/pdbsum/6c1a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6c1a ProSAT]</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=6c1a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6c1a OCA], [http://pdbe.org/6c1a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6c1a RCSB], [http://www.ebi.ac.uk/pdbsum/6c1a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6c1a ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[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/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 ==
Cytosine methylation is a well characterized epigenetic mark and occurs at both CG and non-CG sites in DNA. Both methylated CG (mCG)- and mCH (H = A, C, or T)-containing DNAs, especially mCAC-containing DNAs, are recognized by methyl-CpG-binding protein 2 (MeCP2) to regulate gene expression in neuron development. However, the molecular mechanism involved in the binding of methyl-CpG-binding domain (MBD) of MeCP2 to these different DNA motifs is unclear. Here, we systematically characterized the DNA-binding selectivity of the MBDs in MeCP2 and MBD1-4 with isothermal titration calorimetry-based binding assays, mutagenesis studies, and X-ray crystallography. We found that the MBD domains of MeCP2 and MBD1-4&lt;br /&gt;bind mCG-containing DNAs independently of the sequence outside the mCG dinucleotide. Moreover, some 1 MBDs bound to both methylated and unmethylated CA dinucleotide-&lt;br /&gt;containing DNAs, with a preference for the CAC sequence motif. We also found that MBD domains bind to mCA or nonmethylated CA DNA by recognizing the complementary TG dinucleotide, which is consistent with an overlooked ligand of MeCP2, i.e., the matrix/scaffold attachment regions (MARs/SARs) with a consensus sequence of 5'-GGTGT-3', which was&lt;br /&gt;identified in early 1990s. Our results also explain why MeCP2 exhibits similar binding affinity to both mCAand hmCA-containing dsDNAs. In summary, our results suggest that in addition to mCG sites, unmethylated CA or TG sites also serve as DNA-binding sites for MeCP2 and other MBDcontaining proteins. This discovery expands the genome-wide activity of MBD-containing proteins in gene regulation.


Structural basis for the ability of MBD domains to bind methyl-CG and TG sites in DNA.,Liu K, Xu C, Lei M, Yang A, Loppnau P, Hughes TR, Min J J Biol Chem. 2018 Mar 22. pii: RA118.001785. doi: 10.1074/jbc.RA118.001785. PMID:29567833<ref>PMID:29567833</ref>
==See Also==
 
*[[Methyl CpG binding protein 3D structures|Methyl CpG binding protein 3D structures]]
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6c1a" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Arrowsmith, C H]]
[[Category: Large Structures]]
[[Category: Bountra, C]]
[[Category: Synthetic construct]]
[[Category: Edwards, A M]]
[[Category: Arrowsmith CH]]
[[Category: Liu, K]]
[[Category: Bountra C]]
[[Category: Min, J]]
[[Category: Edwards AM]]
[[Category: Structural genomic]]
[[Category: Liu K]]
[[Category: Tempel, W]]
[[Category: Min J]]
[[Category: Xu, C]]
[[Category: Tempel W]]
[[Category: Dna binding]]
[[Category: Xu C]]
[[Category: Dna binding protein-dna complex]]
[[Category: Dna methylation]]
[[Category: Sgc]]

Latest revision as of 17:25, 13 March 2024

MBD2 in complex with methylated DNAMBD2 in complex with methylated DNA

Structural highlights

6c1a is a 8 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.05Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.[1] [2] [3] [4] [5] [6]

See Also

References

  1. ↑ 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
  2. ↑ 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
  3. ↑ 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
  4. ↑ 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
  5. ↑ 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
  6. ↑ 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

6c1a, resolution 2.05Å

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