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Updated: Jan 23, 2026
PIP-on-a-chip: A Label-free Study of Protein-phosphoinositide Interactions
Published on: July 27, 2017
Structure of PCNA in complex with DNMT1 PIP box reveals the basis for the molecular mechanism of the interaction
Tomohiro Jimenji1, Rumie Matsumura1, Satomi Kori1
1Structural Biology Laboratory, Graduate School of Medical Life Science, Yokohama City University, Yokohama, 230-0045, Japan.
Abstract:
DNMT1 is a C5-DNA methyltransferase that plays a pivotal role in DNA methylation maintenance. During early and mid S-phase, DNMT1 accumulates at DNA replication sites by binding to proliferating cell nuclear antigen (PCNA), an essential factor for DNA replication, through a PIP box motif. However, the molecular mechanism by which the DNMT1 PIP box motif binds to PCNA remains unclear. Here, we report the crystal structure of PCNA bound to DNMT1 PIP box peptide. The structure reveals the detailed interaction between PCNA and DNMT1 PIP box; conserved glutamine and hydrophobic/aromatic residues in the PIP box are recognized by the Q- and hydrophobic pockets of PCNA, respectively. The structure also shows novel intramolecular interactions within the PIP box motif, which stabilize the helix conformation in the PIP box. Our data provide structural insight into the recruitment of DNMT1 to replication sites by PCNA.
Insights
DNA methyltransferase DNMT1 binds to proliferating cell nuclear antigen (PCNA) at replication sites via a PIP box motif. This study reveals the crystal structure of PCNA bound to the DNMT1 PIP box, clarifying their interaction mechanism.
Area of Science:
- Molecular Biology
- Structural Biology
- Epigenetics
Background:
- DNA methyltransferase 1 (DNMT1) maintains DNA methylation patterns.
- DNMT1 localizes to DNA replication sites during S-phase by interacting with proliferating cell nuclear antigen (PCNA).
- The precise molecular mechanism of DNMT1-PCNA interaction via the PIP box motif is not fully understood.
Purpose of the Study:
- To elucidate the structural basis of the interaction between the DNMT1 PIP box motif and PCNA.
- To provide insights into the recruitment of DNMT1 to DNA replication sites.
Main Methods:
- X-ray crystallography to determine the structure of PCNA bound to a DNMT1 PIP box peptide.
- Analysis of protein-protein interactions at the molecular level.
Main Results:
- The crystal structure reveals specific interactions between the DNMT1 PIP box and PCNA.
- Conserved glutamine and hydrophobic/aromatic residues of the PIP box engage with PCNA's Q- and hydrophobic pockets.
- Novel intramolecular interactions within the PIP box stabilize its helical conformation.
Conclusions:
- The study provides a detailed structural understanding of how the DNMT1 PIP box binds to PCNA.
- This structural insight clarifies the mechanism for recruiting DNMT1 to DNA replication sites, crucial for DNA methylation maintenance.
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