6cc8: Difference between revisions
New page: '''Unreleased structure''' The entry 6cc8 is ON HOLD until Apr 04 2019 Authors: Liu, K., Tempel, W., Bountra, C., Arrowsmith, C.H., Edwards, A.M., Min, J., Structural Genomics Consortiu... |
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The | ==Crystal structure MBD3 MBD domain in complex with methylated CpG DNA== | ||
<StructureSection load='6cc8' size='340' side='right'caption='[[6cc8]], [[Resolution|resolution]] 1.95Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6cc8]] is a 6 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=6CC8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6CC8 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.95Å</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6cc8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cc8 OCA], [https://pdbe.org/6cc8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6cc8 RCSB], [https://www.ebi.ac.uk/pdbsum/6cc8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6cc8 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/MBD3_HUMAN MBD3_HUMAN] Acts as transcriptional repressor and plays a role in gene silencing. Does not bind DNA by itself. Recruits histone deacetylases and DNA methyltransferases.<ref>PMID:9774669</ref> <ref>PMID:10947852</ref> <ref>PMID:12124384</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The MBD3, a methyl-CpG-binding domain (MBD)-containing protein, is a core subunit of the Mi-2/NuRD complex. Recent reports show that MBD3 recognizes both methylated CG (mCG)- and hydroxymethylated CG (hmCG)-containing DNA, with a preference for hmCG. However, whether the MBD3-MBD indeed has methyl-CG-binding ability is controversial. In this study, we provided the structural basis to support the ability of MBD3-MBD to bind mCG-containing DNA. We found that the MBD3-MBD bound to mCG-containing DNA through two conserved arginine fingers, and preferentially bound to mCG over hmCG, similar to other methyl-CpG-binding MBD proteins. Compared to its closest homolog MBD2, the tyrosine-to-phenylalanine substitution at Phe34 of MBD3 is responsible for a weaker mCG DNA binding ability. Based on the complex structure of MBD3-MBD with a nonpalindromic AmCGC DNA, we suggest that all the mCG-binding MBD domains can recognize mCG-containing DNA without orientation selectivity, consistent with our observations that the sequences outside the mCG dinucleotide do not affect mCG DNA binding significantly. DNA cytosine methylation is evolutionarily conserved in most metazoans, and most invertebrates have only one MBD gene, MBD2/3. We also looked into the mCG DNA binding ability of some invertebrates MBD2/3 and found that the conserved arginine fingers and a conserved structural fold are required for methylated DNA binding by MBD2/3-MBDs in invertebrates. Hence, our results demonstrate that mCG-binding arginine fingers embedded into a conserved structural fold are essential structural features for MBD2/3s binding to methylated DNA among metazoans. | |||
Structural analyses reveal that MBD3 is a methylated CG binder.,Liu K, Lei M, Wu Z, Gan B, Cheng H, Li Y, Min J FEBS J. 2019 Apr 13. doi: 10.1111/febs.14850. PMID:30980593<ref>PMID:30980593</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 6cc8" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: | ==See Also== | ||
[[Category: Edwards | *[[Methyl CpG binding protein 3D structures|Methyl CpG binding protein 3D structures]] | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
[[Category: Tempel | __TOC__ | ||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Synthetic construct]] | |||
[[Category: Arrowsmith CH]] | |||
[[Category: Bountra C]] | |||
[[Category: Edwards AM]] | |||
[[Category: Liu K]] | |||
[[Category: Min J]] | |||
[[Category: Tempel W]] | |||
Latest revision as of 18:00, 4 October 2023
Crystal structure MBD3 MBD domain in complex with methylated CpG DNACrystal structure MBD3 MBD domain in complex with methylated CpG DNA
Structural highlights
FunctionMBD3_HUMAN Acts as transcriptional repressor and plays a role in gene silencing. Does not bind DNA by itself. Recruits histone deacetylases and DNA methyltransferases.[1] [2] [3] Publication Abstract from PubMedThe MBD3, a methyl-CpG-binding domain (MBD)-containing protein, is a core subunit of the Mi-2/NuRD complex. Recent reports show that MBD3 recognizes both methylated CG (mCG)- and hydroxymethylated CG (hmCG)-containing DNA, with a preference for hmCG. However, whether the MBD3-MBD indeed has methyl-CG-binding ability is controversial. In this study, we provided the structural basis to support the ability of MBD3-MBD to bind mCG-containing DNA. We found that the MBD3-MBD bound to mCG-containing DNA through two conserved arginine fingers, and preferentially bound to mCG over hmCG, similar to other methyl-CpG-binding MBD proteins. Compared to its closest homolog MBD2, the tyrosine-to-phenylalanine substitution at Phe34 of MBD3 is responsible for a weaker mCG DNA binding ability. Based on the complex structure of MBD3-MBD with a nonpalindromic AmCGC DNA, we suggest that all the mCG-binding MBD domains can recognize mCG-containing DNA without orientation selectivity, consistent with our observations that the sequences outside the mCG dinucleotide do not affect mCG DNA binding significantly. DNA cytosine methylation is evolutionarily conserved in most metazoans, and most invertebrates have only one MBD gene, MBD2/3. We also looked into the mCG DNA binding ability of some invertebrates MBD2/3 and found that the conserved arginine fingers and a conserved structural fold are required for methylated DNA binding by MBD2/3-MBDs in invertebrates. Hence, our results demonstrate that mCG-binding arginine fingers embedded into a conserved structural fold are essential structural features for MBD2/3s binding to methylated DNA among metazoans. Structural analyses reveal that MBD3 is a methylated CG binder.,Liu K, Lei M, Wu Z, Gan B, Cheng H, Li Y, Min J FEBS J. 2019 Apr 13. doi: 10.1111/febs.14850. PMID:30980593[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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