Design, synthesis, structure and binding properties of PDZ binding, cyclic beta-finger peptides
Sabine Seedorff1, Christian Appelt, Michael Beyermann
1Leibniz-Institut für Molekulare Pharmakologie (FMP), Robert-Rössle-Str. 10, D-13125 Berlin, Germany.
Abstract:
Protein interaction domains (PIDs) play a critical role in signal transduction. One PID of great interest is the PDZ domain, a 100 amino-acid-residue domain. Most PDZ domains recognize short, C-terminal peptide motives. In the heterodimer of the nNOS-PDZ domain and the alpha-syntrophin-PDZ domain, however, one PDZ domain forms a beta-finger that binds to the other PDZ domain. We show here that cyclic peptides derived from the beta-finger of the nNOS-PDZ domain can bind the syntrophin-PDZ domain in the same manner as the whole domain. The structure of three "finger-peptides" of different size has been determined and the binding investigated using calorimetry and NMR-titration experiments.
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