Design, synthesis, structure and binding properties of PDZ binding, cyclic beta-finger peptides.
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.
Seedorff
Sabine
S
Leibniz-Institut für Molekulare Pharmakologie (FMP), Robert-Rössle-Str. 10, D-13125 Berlin, Germany.
Appelt
Christian
C
Beyermann
Michael
M
Schmieder
Peter
P
D000595:Amino Acid Sequence; D049029:Dystrophin-Associated Proteins / Q000737:chemistry; D008969:Molecular Sequence Data; D052248:Nitric Oxide Synthase Type I / Q000138:chemical synthesis / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D054731:PDZ Domains; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry*; D011485:Protein Binding
D049029:Dystrophin-Associated Proteins; D010456:Peptides, Cyclic; C091824:syntrophin; D052248:Nitric Oxide Synthase Type I