Strand Displacement in Coiled‐Coil Structures: Controlled Induction and Reversal of Proximity

• Published in: Angewandte Chemie International Edition Vol. 56; no. 45; pp. 14217 - 14221
• Main Authors: Gröger, Katharina, Gavins, Georgina, Seitz, Oliver
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 06.11.2017
• Edition: International ed. in English
• Subjects: Chromophores; coiled-coil peptides; Coils; Complex formation; Control stability; Fluorescence; molecular recognition; molecular switches; Peptides; protein–protein interactions; Self-assembly; Switching; Syk protein; molecular recognition; peptides; coiled-coil peptides; molecular switches; protein-protein interactions
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201705339

Coiled‐coil peptides are frequently used to create new function upon the self‐assembly of supramolecular complexes. A multitude of coil peptide sequences provides control over the specificity and stability of coiled‐coil complexes. However, comparably little attention has been paid to the development of methods that allow the reversal of complex formation under non‐denaturing conditions. Herein, we present a reversible two‐state switching system. The process involves two peptide molecules for the formation of a size‐mismatched coiled‐coil duplex and a third, disruptor peptide that targets an overhanging end. A real‐time fluorescence assay revealed that the proximity between two chromophores can be switched on and off, repetitively if desired. Showcasing the advantages provided by non‐denaturing conditions, the method permitted control over the bivalent interactions of the tSH2 domain of Syk kinase with a phosphopeptide ligand. Connect and disconnect: A reversible two‐state switching system was developed based on the formation of size‐mismatched and size‐matched coiled‐coil complexes. Interactions between three coiled‐coil peptides allow reversible switching of the optical properties and protein binding of peptide conjugates.