4ZTD

Crystal Structure of Human PCNA in complex with a TRAIP peptide

Summary for 4ZTD

• Entry DOI: 10.2210/pdb4ztd/pdb
• Descriptor: Proliferating cell nuclear antigen, ALA-PHE-GLN-ALA-LYS-LEU-ASP-THR-PHE-LEU-TRP-SER, ALA-GLY-ALA-GLY-ALA, ... (4 entities in total)
• Functional Keywords: pcna, traip, complex, replication
• Biological source: Homo sapiens (Human); More
• Cellular location: Nucleus : P12004
• Total number of polymer chains: 6
• Total formula weight: 86915.10

Authors

Montoya, G.,Mortuza, G.B.,Blanco, F.J.,Ibanez de Opakua, A. (deposition date: 2015-05-14, release date: 2015-12-16, Last modification date: 2024-01-10)

Primary citation

Hoffmann, S.,Smedegaard, S.,Nakamura, K.,Mortuza, G.B.,Raschle, M.,Ibanez de Opakua, A.,Oka, Y.,Feng, Y.,Blanco, F.J.,Mann, M.,Montoya, G.,Groth, A.,Bekker-Jensen, S.,Mailand, N.
TRAIP is a PCNA-binding ubiquitin ligase that protects genome stability after replication stress.
J.Cell Biol., 212:63-75, 2016

PubMed Abstract: Cellular genomes are highly vulnerable to perturbations to chromosomal DNA replication. Proliferating cell nuclear antigen (PCNA), the processivity factor for DNA replication, plays a central role as a platform for recruitment of genome surveillance and DNA repair factors to replication forks, allowing cells to mitigate the threats to genome stability posed by replication stress. We identify the E3 ubiquitin ligase TRAIP as a new factor at active and stressed replication forks that directly interacts with PCNA via a conserved PCNA-interacting peptide (PIP) box motif. We show that TRAIP promotes ATR-dependent checkpoint signaling in human cells by facilitating the generation of RPA-bound single-stranded DNA regions upon replication stress in a manner that critically requires its E3 ligase activity and is potentiated by the PIP box. Consequently, loss of TRAIP function leads to enhanced chromosomal instability and decreased cell survival after replication stress. These findings establish TRAIP as a PCNA-binding ubiquitin ligase with an important role in protecting genome integrity after obstacles to DNA replication.

PubMed: 26711499
DOI: 10.1083/jcb.201506071

Experimental method

X-RAY DIFFRACTION (2.199 Å)