The Mechanism of Binding of the Second PDZ Domain from the Protein Tyrosine Phosphatase-BL to the Adenomatous Polyposis Coli tumor Suppressor

Di Silvio et al., Protein Eng. Des. Sel (2014) - PMID: 24928580

Product(s) used in this publication:  Specialty Peptides

Abstract:

Many biological processes are regulated by the interaction between protein domains and their corresponding binding partners. The PDZ domain is one of the most common protein-protein interaction modules in mammalian cells, whose role is to bind C-terminal sequences of specific targets. The second PDZ domain from the Protein Tyrosine Phosphatase-BL (PDZ2) binds to the C-terminal of Adenomatous Polyposis Coli protein (APC), one of the major tumor suppressor whose task is to regulate cell adhesion and proliferation. Here, we present a detailed kinetics analysis of the interaction between PDZ2 domain and a peptide mimicking the PDZ binding motif of APC. By analyzing data obtained at different experimental conditions, we propose a plausible mechanism for binding. Furthermore, a comparison between the dissociation rate constant measured by different methodologies allow us to identify an additional kinetic step, which is likely to arise from a conformational change of PDZ2 occurring after binding. The data are discussed on the light of previous work on PDZ domains.

© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

KEYWORDS:

kinetics; peptide binding; protein–protein interaction

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