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.
https://hal-riip.archives-ouvertes.fr/pasteur-01181359
Contributor : Istituto Pasteur Fondazione Cenci Bolognetti
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Eva Di Silvio, Daniela Bonetti, Angelo Toto, Angela Morrone, Stefano Gianni. The mechanism of binding of the second PDZ domain from the Protein Tyrosine Phosphatase-BL to the Adenomatous Polyposis Coli tumor suppressor.. Protein Engineering, Design and Selection, Oxford University Press (OUP), 2014, 27 (8), pp.249-53. ⟨10.1093/protein/gzu022⟩. ⟨pasteur-01181359⟩
