5MLO

Crystal structure of human PCNA in complex with ZRANB3 PIP box peptide

Summary for 5MLO

• Entry DOI: 10.2210/pdb5mlo/pdb
• Descriptor: Proliferating cell nuclear antigen, ZRANB3 PIP box peptide, SODIUM ION, ... (4 entities in total)
• Functional Keywords: endonuclease, metalloprotein, pcna, dna-binding, hydrolase
• Biological source: Homo sapiens (Human); More
• Cellular location: Nucleus : P12004
• Total number of polymer chains: 6
• Total formula weight: 92155.57

Authors

Ariza, A. (deposition date: 2016-12-07, release date: 2017-06-28, Last modification date: 2024-01-17)

Primary citation

Sebesta, M.,Cooper, C.D.O.,Ariza, A.,Carnie, C.J.,Ahel, D.
Structural insights into the function of ZRANB3 in replication stress response.
Nat Commun, 8:15847-15847, 2017

PubMed Abstract: Strategies to resolve replication blocks are critical for the maintenance of genome stability. Among the factors implicated in the replication stress response is the ATP-dependent endonuclease ZRANB3. Here, we present the structure of the ZRANB3 HNH (His-Asn-His) endonuclease domain and provide a detailed analysis of its activity. We further define PCNA as a key regulator of ZRANB3 function, which recruits ZRANB3 to stalled replication forks and stimulates its endonuclease activity. Finally, we present the co-crystal structures of PCNA with two specific motifs in ZRANB3: the PIP box and the APIM motif. Our data provide important structural insights into the PCNA-APIM interaction, and reveal unexpected similarities between the PIP box and the APIM motif. We propose that PCNA and ATP-dependency serve as a multi-layered regulatory mechanism that modulates ZRANB3 activity at replication forks. Importantly, our findings allow us to interpret the functional significance of cancer associated ZRANB3 mutations.

PubMed: 28621305
DOI: 10.1038/ncomms15847

Experimental method

X-RAY DIFFRACTION (1.96 Å)