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Methyl CpG binding protein

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<StructureSection load='4evv' size='340' side='right' caption='Structure of mouse MBD4 glycosylate domain complex with DNA containing mismatch, ethylene glycol and Ni+2 ion (green) (PDB code [[4evv]]).' scene=''>
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<StructureSection load='4evv' size='350' side='right' caption='Structure of mouse MBD4 glycosylate domain complex with DNA containing mismatch, ethylene glycol and Ni+2 ion (green) (PDB code [[4evv]]).' scene='59/597003/Cv/1'>
== Function ==
== Function ==
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'''Methyl CpG binding proteins''' are called MBD1 to MBD4 and contain a methyl-CpG binding domain (MBD) which binds to methylated DNA.<br />
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'''Methyl CpG binding proteins''' are called MBD1 to MBD4 and contain a methyl-CpG binding domain (MBD) which binds to methylated DNA<ref>PMID:11746232</ref>.<br />
• '''MBD1''' is a transcription regulator. It reverts methylated cytosine bases to cytosine.<br />
• '''MBD1''' is a transcription regulator. It reverts methylated cytosine bases to cytosine.<br />
• '''MBD2''' is part of the MeCP1 complex which contains also NuRD. MBD2 recruits histone deacetylases and DNA methyltransferases. MBD2 functions as a scaffold protein promoting repression.<br />
• '''MBD2''' is part of the MeCP1 complex which contains also NuRD. MBD2 recruits histone deacetylases and DNA methyltransferases. MBD2 functions as a scaffold protein promoting repression.<br />
• '''MBD3''' binds to hydroxymethylated DNA.<br />
• '''MBD3''' binds to hydroxymethylated DNA.<br />
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• '''MBD4''' has a G:T mipair-specific activity.<br />
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• '''MBD4''' has a G:T mispair-specific activity.<br />
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• '''Methyl CpG binding protein 2''' (MeCP2) is present in mature nerve cells and is involved in turning off several genes. For more details see [[Methyl CpG Binding Protein 2]].<br />
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• '''Methyl CpG binding protein 2''' (MeCP2) is present in mature nerve cells and is involved in turning off several genes. For more details see [[Methyl CpG Binding Protein 2]] and [[Rett Syndrome Protein]].<br />
== Disease ==
== Disease ==
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Mutations in MBD2 are involved in Rett syndrome<ref>PMID:11738862</ref>.
== Relevance ==
== Relevance ==
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MBD1 has a role in lung, prostate, pancreatic, colorectal cancers and promyelocytic leukemia. MBD2 has a role in lung, prostate, renal, colorectal cancers. MBD3 has a role in lung, prostate, ovarian cancers and promyelocytic leukemia. MBD4 has a role in gastric, liver and colorectal cancers.
== Structural highlights ==
== Structural highlights ==
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</StructureSection>
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<scene name='59/597003/Cv/3'>Thymine from the mismatched G:T pair flips out from the DNA strand and interchelates with MBD4 residues Lys and Leu</scene><ref>PMID:22740654</ref>.
==3D structures of methyl CpG binding protein==
==3D structures of methyl CpG binding protein==
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[[Methyl CpG binding protein 3D structures]]
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Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
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</StructureSection>
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{{#tree:id=OrganizedByTopic|openlevels=0|
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*Methyl CpG binding protein 1 (MBD1)
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**[[1ig4]] – hMBD1 MBD domain + DNA – human – NMR<br />
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**[[1d9n]] - hMBD1 MBD domain – NMR
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*Methyl CpG binding protein 2 (MBD2)
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**[[2l2l]] - hMBD2 coiled-coil domain + transcriptional repressor p66-α coiled-coil domain – NMR<br />
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*Methyl CpG binding protein 3 (MBD3)
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**[[2mb7]] – hMBD3 MBD domain – NMR<br />
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*Methyl CpG binding protein 4 (MBD4)
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**[[1ngn]] - MBD4 glycosylate domain – mouse<br />
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**[[3iho]], [[4e9e]] – hMBD4 glycosylate domain<br />
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**[[4e9g]] – hMBD4 glycosylate domain + DNA <br />
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**[[4dk9]], [[4e9f]] – hMBD4 glycosylate domain + DNA containing abasic dideoxyribose<br />
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**[[4ew4]] – mMBD4 glycosylate domain + DNA containing abasic dideoxyribose<br />
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**[[4evv]] – mMBD4 glycosylate domain + DNA containing mismatch<br />
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**[[4ew0]] – mMBD4 glycosylate domain (mutant) + DNA containing hydroxymethyluracil<br />
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**[[4e9h]], [[4ea4]], [[4ea5]] – hMBD4 glycosylate domain (mutant) + DNA containing hydroxymethyluracil<br />
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**[[3vxv]], [[3vxx]], [[3vyb]], [[3vyq]] – mMBD4 MBD + DNA containing cytidine derivative<br />
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**[[4lg7]], [[2moe]] – hMBD4 MBD + DNA containing cytidine derivative<br />
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**[[4ofa]], [[4ofe]], [[4ofh]] – hMBD4 MBD (mutant) + DNA containing mismatch<br />
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*Methyl CpG binding protein 2 (MeCP2)
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**[[1qk9]] - hMeCP2 MBD domain – NMR<br />
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**[[3c2i]] – hMeCP2 MBD domain (mutant) + DNA<br />
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**[[1ub1]] – cMeCP2 attachment-region binding domain – chicken – NMR<br />
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**[[2ky8]] – cMBD4 MBD + DNA containing cytidine and uridine derivatives - NMR<br />
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}}
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== References ==
== References ==

Current revision

Structure of mouse MBD4 glycosylate domain complex with DNA containing mismatch, ethylene glycol and Ni+2 ion (green) (PDB code 4evv).

Drag the structure with the mouse to rotate

References

  1. ↑ Wade PA. Methyl CpG-binding proteins and transcriptional repression. Bioessays. 2001 Dec;23(12):1131-7. PMID:11746232 doi:http://dx.doi.org/10.1002/bies.10008
  2. ↑ Van den Veyver IB, Zoghbi HY. Mutations in the gene encoding methyl-CpG-binding protein 2 cause Rett syndrome. Brain Dev. 2001 Dec;23 Suppl 1:S147-51. PMID:11738862
  3. ↑ Hashimoto H, Zhang X, Cheng X. Excision of thymine and 5-hydroxymethyluracil by the MBD4 DNA glycosylase domain: structural basis and implications for active DNA demethylation. Nucleic Acids Res. 2012 Jun 27. PMID:22740654 doi:10.1093/nar/gks628

Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky

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