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Flexibility of PCNA-protein interface accommodates differential binding partners.

ABSTRACT: The expanding roles of PCNA in functional assembly of DNA replication and repair complexes motivated investigation of the structural and dynamic properties guiding specificity of PCNA-protein interactions. A series of biochemical and computational analyses were combined to evaluate the PIP Box recognition features impacting complex formation. The results indicate subtle differences in topological and molecular descriptors distinguishing both affinity and stoichiometry of binding among PCNA-peptide complexes through cooperative effects. These features were validated using peptide mimics of p85? and Akt, two previously unreported PCNA binding partners. This study characterizes for the first time a reverse PIP Box interaction with PCNA. Small molecule ligand binding at the PIP Box interaction site confirmed the adaptive nature of the protein in dictating overall shape and implicates allosterism in transmitting biological effects.

SUBMITTER: Pedley AM

PROVIDER: S-EPMC4103810 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Flexibility of PCNA-protein interface accommodates differential binding partners.

Pedley Anthony M AM Lill Markus A MA Davisson V Jo VJ

PloS one 20140718 7

The expanding roles of PCNA in functional assembly of DNA replication and repair complexes motivated investigation of the structural and dynamic properties guiding specificity of PCNA-protein interactions. A series of biochemical and computational analyses were combined to evaluate the PIP Box recognition features impacting complex formation. The results indicate subtle differences in topological and molecular descriptors distinguishing both affinity and stoichiometry of binding among PCNA-pepti ...[more]

PMID: 25036435

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