Unlocking the PIP-box: A peptide library reveals interactions that drive high-affinity binding to human PCNA.

ABSTRACT: The human sliding clamp, Proliferating Cell Nuclear Antigen (hPCNA), interacts with over 200 proteins through a conserved binding motif, the PIP-box, to orchestrate DNA replication and repair. It is not clear how changes to the features of a PIP-box modulate protein binding and thus how they fine-tune downstream processes. Here, we present a systematic study of each position within the PIP-box to reveal how hPCNA-interacting peptides bind with drastically varied affinities. We synthesized a series of 27 peptides derived from the native protein p21 with small PIP-box modifications and another series of 19 peptides containing PIP-box binding motifs from other proteins. The hPCNA-binding affinity of all peptides, characterized as K_D values determined by surface plasmon resonance, s

SUBMITTER: Horsfall AJ 

PROVIDER: S-EPMC8191301 | biostudies-literature | 2021 Jan-Jun

REPOSITORIES: biostudies-literature