View source for 2mwp


==Solution structure of 53BP1 tandem Tudor domains in complex with a p53K382me2 peptide==
<StructureSection load='2mwp' size='340' side='right'caption='[[2mwp]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2mwp]] is a 2 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=2MWP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MWP FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MLY:N-DIMETHYL-LYSINE'>MLY</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=2mwp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mwp OCA], [https://pdbe.org/2mwp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mwp RCSB], [https://www.ebi.ac.uk/pdbsum/2mwp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mwp ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/TP53B_HUMAN TP53B_HUMAN] Note=A chromosomal aberration involving TP53BP1 is found in a form of myeloproliferative disorder chronic with eosinophilia. Translocation t(5;15)(q33;q22) with PDGFRB creating a TP53BP1-PDGFRB fusion protein.
== Function ==
[https://www.uniprot.org/uniprot/TP53B_HUMAN TP53B_HUMAN] Plays a key role in the response to DNA damage. May have a role in checkpoint signaling during mitosis. Enhances TP53-mediated transcriptional activation.<ref>PMID:12364621</ref> <ref>PMID:17190600</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
p53 is dynamically regulated through various posttranslational modifications (PTMs), which differentially modulate its function and stability. The dimethylated marks p53K370me2 and p53K382me2 are associated with p53 activation or stabilization and both are recognized by the tandem Tudor domain (TTD) of 53BP1, a p53 cofactor. Here we detail the molecular mechanisms for the recognition of p53K370me2 and p53K382me2 by 53BP1. The solution structures of TTD in complex with the p53K370me2 and p53K382me2 peptides show a remarkable plasticity of 53BP1 in accommodating these diverse dimethyllysine-containing sequences. We demonstrate that dimeric TTDs are capable of interacting with the two PTMs on a single p53K370me2K382me2 peptide, greatly strengthening the 53BP1-p53 interaction. Analysis of binding affinities of TTD toward methylated p53 and histones reveals strong preference of 53BP1 for p53K382me2, H4K20me2, and H3K36me2 and suggests a possible role of multivalent contacts of 53BP1 in p53 targeting to and accumulation at the sites of DNA damage.

Structural Plasticity of Methyllysine Recognition by the Tandem Tudor Domain of 53BP1.,Tong Q, Cui G, Botuyan MV, Rothbart SB, Hayashi R, Musselman CA, Singh N, Appella E, Strahl BD, Mer G, Kutateladze TG Structure. 2015 Jan 8. pii: S0969-2126(14)00406-7. doi:, 10.1016/j.str.2014.11.013. PMID:25579814<ref>PMID:25579814</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2mwp" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Botuyan MV]]
[[Category: Cui G]]
[[Category: Mer G]]