Control of protein-protein-interactions through conformational changes induced by light: photo-switchable ligand molecules for PDZ domain

Cytoplasmatic proteins that are involved in signal transduction are commonly constructed of modular domains that either have a catalytic function (e.g. kinases) or belong to the protein interaction domains (PIDs). The latter play a critical role in the assembly of protein complexes that control the complex cellular behavior. One PID of great interest is the PDZ domain, a 100 amino-acid-residue domain. It frequently occurs as multiple copies in cytoplasmatic proteins and is often involved in the assembly of molecular complexes near the plasma membrane. While most PDZ-domains recognize short, C-terminal peptide motifs, some do also recognize internal binding motives like loops. The present project aims at the design of ligands for both types of PDZ binding modes, using the syntrophin PDZ domain as the protein partner. The ligands will be cyclic peptides that contain a photosensitive, artificial amino acid. This will allow a control of conformation and thus activity of the peptide ligands via the irradiation of light. The artificial amino acids as well as the peptides will be synthesized, the PDZ domain will be expressed in E.coli, the binding of the ligands to the PDZ domain will be quantified and the structures of the free ligands and the ligand-protein complexes will be determined using NMR spectroscopy.


C. Hoppmann*; P. Schmieder; P. Domaing; G. Vogelreiter; J. Eichhorst; B. Wiesner; I. Morano; K. Rück-Braun; M. Beyermann; "Photocontrol of Contracting Muscle Fibers"; Angew. Chem. Int. Ed. Engl. 50, 7699-7702 (2011); Angew. Chem. 123, 7841–7845 (2011)

DOI: 10.1002/anie.201101398 / DOI: 10.1002/ange.201101398

S. Seedorff; C. Appelt; M. Beyermann; P. Schmieder*; "Design, synthesis, structure and binding properties of PDZ binding, cyclic beta-finger peptides"; Biochem. Biophys. Res. Commun. 395, 535-539 (2010)

DOI: 10.1016/j.bbrc.2010.04.060

C. Hoppmann C; S. Seedorff; A. Richter; H. Fabian; P. Schmieder; K. Rück-Braun; M. Beyermann*; "Light-directed protein binding of a biologically relevant beta-sheet"; Angew. Chem. Int. Ed. Engl. 48, 6636-6639 (2009); Angew. Chem. 121, 6763-6766 (2009)

DOI: 10.1002/anie.200901933 / DOI: 10.1002/ange.200901933

last changes 01.03.2013, Peter Schmieder