2mb7: Difference between revisions
New page: '''Unreleased structure''' The entry 2mb7 is ON HOLD until Paper Publication Authors: Williams Jr., D.C., Scarsdale, J.N. Description: Solution structure of MBD3 methylcytosine binding... |
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==Solution structure of MBD3 methylcytosine binding domain== | |||
<StructureSection load='2mb7' size='340' side='right'caption='[[2mb7]]' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2mb7]] is a 1 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=2MB7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MB7 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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2mb7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mb7 OCA], [https://pdbe.org/2mb7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mb7 RCSB], [https://www.ebi.ac.uk/pdbsum/2mb7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mb7 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 == | |||
Although highly homologous to other methylcytosine binding domain (MBD) proteins, MBD3 does not selectively bind methylated DNA and thus the functional role of MBD3 remains in question. To explore the structural basis of its binding properties and potential function, we characterized the solution structure and binding distribution of the MBD3 MBD on hydroxymethylated, methylated and unmethylated DNA. The overall fold of this domain is very similar to other MBDs, yet a key loop involved in DNA binding is more disordered than previously observed. Specific recognition of methylated DNA constrains the structure of this loop and results in large chemical shift changes in NMR spectra. Based on these spectral changes, we show that MBD3 preferentially localizes to methylated and, to a lesser degree, unmethylated cytosine-guanosine dinucleotides (CpGs), yet does not distinguish between hydroxymethylated and unmethylated sites. Measuring residual dipolar couplings (RDCs) for the different bound states clearly shows that the MBD3 structure does not change between methylation specific and non-specific binding modes. Furthermore, RDCs measured for MBD3 bound to methylated DNA can be described by a linear combination of those for the methylation and non-specific binding modes, confirming the preferential localization to methylated sites. The highly homologous MBD2 protein shows similar but much stronger localization to methylated as well as unmethylated CpGs. Together, these data establish the structural basis for the relative distribution of MBD2 and MBD3 on genomic DNA and their observed occupancy at active and inactive CpG-rich promoters. | |||
Probing the Dynamic Distribution of Bound States for Methyl-cytosine Binding Domains on DNA.,Cramer JM, Scarsdale JN, Walavalkar NM, Buchwald WA, Ginder GD, Williams DC Jr J Biol Chem. 2013 Dec 4. PMID:24307175<ref>PMID:24307175</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2mb7" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Methyl CpG binding protein 3D structures|Methyl CpG binding protein 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Scarsdale JN]] | |||
[[Category: Williams Jr DC]] | |||