2ZVK

Crystal structure of PCNA in complex with DNA polymerase eta fragment


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.286 
  • R-Value Work: 0.215 
  • R-Value Observed: 0.218 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Structural Basis for Novel Interactions between Human Translesion Synthesis Polymerases and Proliferating Cell Nuclear Antigen

Hishiki, A.Hashimoto, H.Hanafusa, T.Kamei, K.Ohashi, E.Shimizu, T.Ohmori, H.Sato, M.

(2009) J Biol Chem 284: 10552-10560

  • DOI: https://doi.org/10.1074/jbc.M809745200
  • Primary Citation of Related Structures:  
    2ZVK, 2ZVL, 2ZVM

  • PubMed Abstract: 

    Translesion synthesis (TLS) is a DNA damage tolerance mechanism that allows continued DNA synthesis, even in the presence of damaged DNA templates. Mammals have multiple DNA polymerases specialized for TLS, including Poleta, Poliota, and Polkappa. These enzymes show preferential bypass for different lesions. Proliferating cell nuclear antigen (PCNA), which functions as a sliding clamp for the replicative polymerase Poldelta, also interacts with the three TLS polymerases. Although many PCNA-binding proteins have a highly conserved sequence termed the PCNA-interacting protein box (PIP-box), Poleta, Poliota, and Polkappa have a noncanonical PIP-box sequence. In response to DNA damage, Lys-164 of PCNA undergoes ubiquitination by the RAD6-RAD18 complex, and the ubiquitination is considered to facilitate TLS. Consistent with this, these three TLS polymerases have one or two ubiquitin binding domains and are recruited to replication forks via interactions with ubiquitinated PCNA involving the noncanonical PIP-box and ubiquitin binding domain. However, it is unclear how these TLS polymerases interact with PCNA. To address the structural basis for interactions between different TLS polymerases and PCNA, we determined crystal structures of PCNA bound to peptides containing the noncanonical PIP-box of these polymerases. We show that the three PIP-box peptides interact with PCNA in different ways, both from one another and from canonical PIP-box peptides. Especially, the PIP-box of Poliota adopts a novel structure. Furthermore, these structures enable us to speculate how these TLS polymerases interact with Lys-164-monoubiquitinated PCNA. Our results will provide clues to understanding the mechanism of preferential recruitment of TLS polymerases to the stalled forks.


  • Organizational Affiliation

    International Graduate School of Arts and Sciences, Yokohama City University, 1-7-29 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Proliferating cell nuclear antigenA,
C [auth B],
E [auth C]
261Homo sapiensMutation(s): 0 
Gene Names: PCNA
UniProt & NIH Common Fund Data Resources
Find proteins for P12004 (Homo sapiens)
Explore P12004 
Go to UniProtKB:  P12004
PHAROS:  P12004
GTEx:  ENSG00000132646 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP12004
Sequence Annotations
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  • Reference Sequence

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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
DNA polymerase etaB [auth U],
D [auth V],
F [auth W]
21N/AMutation(s): 0 
EC: 2.7.7.7
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.286 
  • R-Value Work: 0.215 
  • R-Value Observed: 0.218 
  • Space Group: P 43 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 82.027α = 90
b = 82.027β = 90
c = 310.443γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
ADSCdata collection
HKL-2000data reduction
HKL-2000data scaling
MOLREPphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2009-02-10
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Advisory, Version format compliance
  • Version 1.2: 2023-11-01
    Changes: Data collection, Database references, Refinement description