2MWP

Solution structure of 53BP1 tandem Tudor domains in complex with a p53K382me2 peptide


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 200 
  • Conformers Submitted: 20 
  • Selection Criteria: structures with the lowest energy 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Structural Plasticity of Methyllysine Recognition by the Tandem Tudor Domain of 53BP1.

Tong, Q.Cui, G.Botuyan, M.V.Rothbart, S.B.Hayashi, R.Musselman, C.A.Singh, N.Appella, E.Strahl, B.D.Mer, G.Kutateladze, T.G.

(2015) Structure 23: 312-321

  • DOI: https://doi.org/10.1016/j.str.2014.11.013
  • Primary Citation of Related Structures:  
    2MWO, 2MWP

  • PubMed Abstract: 

    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.


  • Organizational Affiliation

    Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Tumor suppressor p53-binding protein 1123Homo sapiensMutation(s): 0 
Gene Names: TP53BP1
UniProt & NIH Common Fund Data Resources
Find proteins for Q12888 (Homo sapiens)
Explore Q12888 
Go to UniProtKB:  Q12888
PHAROS:  Q12888
GTEx:  ENSG00000067369 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ12888
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Cellular tumor antigen p5312Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P04637 (Homo sapiens)
Explore P04637 
Go to UniProtKB:  P04637
PHAROS:  P04637
GTEx:  ENSG00000141510 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP04637
Sequence Annotations
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  • Reference Sequence
Small Molecules
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
MLY
Query on MLY
B
L-PEPTIDE LINKINGC8 H18 N2 O2LYS
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 200 
  • Conformers Submitted: 20 
  • Selection Criteria: structures with the lowest energy 

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2014-12-10
    Type: Initial release
  • Version 1.1: 2015-01-21
    Changes: Database references
  • Version 1.2: 2015-03-18
    Changes: Database references