6RMM

Crystal structure of TOPBP1 BRCT4,5 in complex with a 53BP1 phosphopeptide


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.53 Å
  • R-Value Free: 0.234 
  • R-Value Work: 0.221 
  • R-Value Observed: 0.222 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Phosphorylation-mediated interactions with TOPBP1 couple 53BP1 and 9-1-1 to control the G1 DNA damage checkpoint.

Bigot, N.Day, M.Baldock, R.A.Watts, F.Z.Oliver, A.W.Pearl, L.H.

(2019) Elife 8

  • DOI: https://doi.org/10.7554/eLife.44353
  • Primary Citation of Related Structures:  
    6RML, 6RMM

  • PubMed Abstract: 

    Coordination of the cellular response to DNA damage is organised by multi-domain 'scaffold' proteins, including 53BP1 and TOPBP1, which recognise post-translational modifications such as phosphorylation, methylation and ubiquitylation on other proteins, and are themselves carriers of such regulatory signals. Here we show that the DNA damage checkpoint regulating S-phase entry is controlled by a phosphorylation-dependent interaction of 53BP1 and TOPBP1. BRCT domains of TOPBP1 selectively bind conserved phosphorylation sites in the N-terminus of 53BP1. Mutation of these sites does not affect formation of 53BP1 or ATM foci following DNA damage, but abolishes recruitment of TOPBP1, ATR and CHK1 to 53BP1 damage foci, abrogating cell cycle arrest and permitting progression into S-phase. TOPBP1 interaction with 53BP1 is structurally complimentary to its interaction with RAD9-RAD1-HUS1, allowing these damage recognition factors to bind simultaneously to the same TOPBP1 molecule and cooperate in ATR activation in the G1 DNA damage checkpoint.


  • Organizational Affiliation

    Cancer Research UK DNA Repair Enzymes Group, Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Brighton, United Kingdom.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
DNA topoisomerase 2-binding protein 1
A, B, C, D
196Homo sapiensMutation(s): 0 
Gene Names: TOPBP1KIAA0259
UniProt & NIH Common Fund Data Resources
Find proteins for Q92547 (Homo sapiens)
Explore Q92547 
Go to UniProtKB:  Q92547
PHAROS:  Q92547
GTEx:  ENSG00000163781 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ92547
Sequence Annotations
Expand
  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
53BP1E [auth P],
F [auth R]
15Homo sapiensMutation(s): 0 
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
Expand
  • Reference Sequence
Small Molecules
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
SEP
Query on SEP
E [auth P],
F [auth R]
L-PEPTIDE LINKINGC3 H8 N O6 PSER
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.53 Å
  • R-Value Free: 0.234 
  • R-Value Work: 0.221 
  • R-Value Observed: 0.222 
  • Space Group: P 65 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 134.81α = 90
b = 134.81β = 90
c = 303.02γ = 120
Software Package:
Software NamePurpose
PHENIXrefinement
xia2data reduction
Aimlessdata scaling
PHASERphasing

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Cancer Research UKUnited KingdomC302/A14532

Revision History  (Full details and data files)

  • Version 1.0: 2019-06-12
    Type: Initial release
  • Version 1.1: 2019-08-21
    Changes: Data collection
  • Version 1.2: 2024-01-24
    Changes: Data collection, Database references, Refinement description