This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

1ig4

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 09:29, 10 January 2018

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

Structural highlights

1ig4 is a 3 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
NonStd Res:
Gene:	MBD1 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9] ^[10]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

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.

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^[11]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Cross SH, Meehan RR, Nan X, Bird A. A component of the transcriptional repressor MeCP1 shares a motif with DNA methyltransferase and HRX proteins. Nat Genet. 1997 Jul;16(3):256-9. PMID:9207790 doi:http://dx.doi.org/10.1038/ng0797-256
↑ Fujita N, Takebayashi S, Okumura K, Kudo S, Chiba T, Saya H, Nakao M. Methylation-mediated transcriptional silencing in euchromatin by methyl-CpG binding protein MBD1 isoforms. Mol Cell Biol. 1999 Sep;19(9):6415-26. PMID:10454587
↑ 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
↑ Ng HH, Jeppesen P, Bird A. Active repression of methylated genes by the chromosomal protein MBD1. Mol Cell Biol. 2000 Feb;20(4):1394-406. PMID:10648624
↑ Fujita N, Watanabe S, Ichimura T, Tsuruzoe S, Shinkai Y, Tachibana M, Chiba T, Nakao M. Methyl-CpG binding domain 1 (MBD1) interacts with the Suv39h1-HP1 heterochromatic complex for DNA methylation-based transcriptional repression. J Biol Chem. 2003 Jun 27;278(26):24132-8. Epub 2003 Apr 23. PMID:12711603 doi:http://dx.doi.org/10.1074/jbc.M302283200
↑ Fujita N, Watanabe S, Ichimura T, Ohkuma Y, Chiba T, Saya H, Nakao M. MCAF mediates MBD1-dependent transcriptional repression. Mol Cell Biol. 2003 Apr;23(8):2834-43. PMID:12665582
↑ Reese BE, Bachman KE, Baylin SB, Rountree MR. The methyl-CpG binding protein MBD1 interacts with the p150 subunit of chromatin assembly factor 1. Mol Cell Biol. 2003 May;23(9):3226-36. PMID:12697822
↑ Ghoshal K, Majumder S, Datta J, Motiwala T, Bai S, Sharma SM, Frankel W, Jacob ST. Role of human ribosomal RNA (rRNA) promoter methylation and of methyl-CpG-binding protein MBD2 in the suppression of rRNA gene expression. J Biol Chem. 2004 Feb 20;279(8):6783-93. Epub 2003 Nov 10. PMID:14610093 doi:http://dx.doi.org/10.1074/jbc.M309393200
↑ Sarraf SA, Stancheva I. Methyl-CpG binding protein MBD1 couples histone H3 methylation at lysine 9 by SETDB1 to DNA replication and chromatin assembly. Mol Cell. 2004 Aug 27;15(4):595-605. PMID:15327775 doi:http://dx.doi.org/10.1016/j.molcel.2004.06.043
↑ Watanabe S, Ichimura T, Fujita N, Tsuruzoe S, Ohki I, Shirakawa M, Kawasuji M, Nakao M. Methylated DNA-binding domain 1 and methylpurine-DNA glycosylase link transcriptional repression and DNA repair in chromatin. Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):12859-64. Epub 2003 Oct 10. PMID:14555760 doi:http://dx.doi.org/10.1073/pnas.2131819100
↑ Ohki I, Shimotake N, Fujita N, Jee J, Ikegami T, Nakao M, Shirakawa M. Solution structure of the methyl-CpG binding domain of human MBD1 in complex with methylated DNA. Cell. 2001 May 18;105(4):487-97. PMID:11371345

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1ig4"

@@ Line 1: / Line 1: @@
 ==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]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
@@ Line 5: / Line 6: @@
 </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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MBD1 ([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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ig4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ig4 OCA], [http://pdbe.org/1ig4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1ig4 RCSB], [http://www.ebi.ac.uk/pdbsum/1ig4 PDBsum]</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=1ig4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ig4 OCA], [http://pdbe.org/1ig4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1ig4 RCSB], [http://www.ebi.ac.uk/pdbsum/1ig4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1ig4 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 13: / Line 14: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ig/1ig4_consurf.spt"</scriptWhenChecked>
+    <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>
@@ Line 28: / Line 29: @@
 </div>
 <div class="pdbe-citations 1ig4" style="background-color:#fffaf0;"></div>
-==See Also==
-*[[Methyl CpG binding protein|Methyl CpG binding protein]]
 == References ==
 <references/>

1ig4

From Proteopedia

Revision as of 09:29, 10 January 2018

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

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox