Photoswitchable Affinity Clamps: Modulating Protein Activity with Light
University of Chicago
Biochemistry and Molecular Biology
Optogenetics, or the study of using genetically-encoded, light-controllable molecules to manipulate living systems, provides biologists with a powerful way to control and observe cellular behavior The purpose of this experiment is to expand the optogenetic toolbox through the creation of a light-controlled affinity clamp whose binding affinity towards its target can be modulated by light. Affinity clamps are novel binding proteins being developed in the Koide lab that feature a unique clamshell architecture. These clamps are a transformative solution in the quest to develop high affinity reagents that can bind to short, unstuctured peptide segments present in biologically relevant protein molecules, such as post-translational modification sites. Therefore, the coupling of light to allosterically control affinity clamps presents the possibility of a very potent tool that can control cellular behavior. The immediate goal of this project will be proof-of-concept, as light-controllable affinity clamps have never been produced. The creation of such a protein, and ultimately being able to control its behavior in cells through light dependent association and dissociation of the clamp to its targets, will allow us to determine a reliable method to rationally and systematically convert clamps into powerful cellular perturbation tools.