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[[Image:1ig4.gif|left|200px]]
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{{STRUCTURE_1ig4|  PDB=1ig4  |  SCENE=  }}
'''Solution Structure of the Methyl-CpG-Binding Domain of Human MBD1 in Complex with Methylated DNA'''


==Solution Structure of the Methyl-CpG-Binding Domain of Human MBD1 in Complex with Methylated DNA==
<StructureSection load='1ig4' size='340' side='right'caption='[[1ig4]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1ig4]] is a 3 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=1IG4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1IG4 FirstGlance]. <br>
</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='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></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=1ig4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ig4 OCA], [https://pdbe.org/1ig4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ig4 RCSB], [https://www.ebi.ac.uk/pdbsum/1ig4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ig4 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/MBD1_HUMAN MBD1_HUMAN] Transcriptional repressor that binds CpG islands in promoters where the DNA is methylated at position 5 of cytosine within CpG dinucleotides. Binding is abolished by the presence of 7-mG that is produced by DNA damage by methylmethanesulfonate (MMS). Acts as transcriptional repressor and plays a role in gene silencing by recruiting AFT7IP, which in turn recruits factors such as the histone methyltransferase SETDB1. Probably forms a complex with SETDB1 and ATF7IP that represses transcription and couples DNA methylation and histone 'Lys-9' trimethylation. Isoform 1 and isoform 2 can also repress transcription from unmethylated promoters.<ref>PMID:9207790</ref> <ref>PMID:10454587</ref> <ref>PMID:9774669</ref> <ref>PMID:10648624</ref> <ref>PMID:12711603</ref> <ref>PMID:12665582</ref> <ref>PMID:12697822</ref> <ref>PMID:14610093</ref> <ref>PMID:15327775</ref> <ref>PMID:14555760</ref>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ig/1ig4_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1ig4 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
In vertebrates, the biological consequences of DNA methylation are often mediated by protein factors containing conserved methyl-CpG binding domains (MBDs). Mutations in the MBD protein MeCP2 cause the neurodevelopmental disease Rett syndrome. We report here the solution structure of the MBD of the human methylation-dependent transcriptional regulator MBD1 bound to methylated DNA. DNA binding causes a loop in MBD1 to fold into a major and novel DNA binding interface. Recognition of the methyl groups and CG sequence at the methylation site is due to five highly conserved residues that form a hydrophobic patch. The structure indicates how MBD may access nucleosomal DNA without encountering steric interference from core histones, and provides a basis to interpret mutations linked to Rett syndrome in MeCP2.


==Overview==
Solution structure of the methyl-CpG binding domain of human MBD1 in complex with methylated DNA.,Ohki I, Shimotake N, Fujita N, Jee J, Ikegami T, Nakao M, Shirakawa M Cell. 2001 May 18;105(4):487-97. PMID:11371345<ref>PMID:11371345</ref>
In vertebrates, the biological consequences of DNA methylation are often mediated by protein factors containing conserved methyl-CpG binding domains (MBDs). Mutations in the MBD protein MeCP2 cause the neurodevelopmental disease Rett syndrome. We report here the solution structure of the MBD of the human methylation-dependent transcriptional regulator MBD1 bound to methylated DNA. DNA binding causes a loop in MBD1 to fold into a major and novel DNA binding interface. Recognition of the methyl groups and CG sequence at the methylation site is due to five highly conserved residues that form a hydrophobic patch. The structure indicates how MBD may access nucleosomal DNA without encountering steric interference from core histones, and provides a basis to interpret mutations linked to Rett syndrome in MeCP2.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
1IG4 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IG4 OCA].
</div>
<div class="pdbe-citations 1ig4" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
Solution structure of the methyl-CpG binding domain of human MBD1 in complex with methylated DNA., Ohki I, Shimotake N, Fujita N, Jee J, Ikegami T, Nakao M, Shirakawa M, Cell. 2001 May 18;105(4):487-97. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11371345 11371345]
*[[Methyl CpG binding protein 3D structures|Methyl CpG binding protein 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Fujita, N.]]
[[Category: Fujita N]]
[[Category: Ikegami, T.]]
[[Category: Ikegami T]]
[[Category: Jee, J G.]]
[[Category: Jee J-G]]
[[Category: Nakao, M.]]
[[Category: Nakao M]]
[[Category: Ohki, I.]]
[[Category: Ohki I]]
[[Category: Shimotake, N.]]
[[Category: Shimotake N]]
[[Category: Shirakawa, M.]]
[[Category: Shirakawa M]]
[[Category: Alpha-beta]]
[[Category: Double helix]]
[[Category: Protein-dna complex]]
[[Category: Recognition via beta-sheet]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 19:57:47 2008''

Latest revision as of 08:34, 22 May 2024

Solution Structure of the Methyl-CpG-Binding Domain of Human MBD1 in Complex with Methylated DNA

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