Many biological processes depend on protein-protein interactions (PPI) and thus the on-demand regulation of the binding affinity between interacting partners offers exciting possibilities in both basic and applied research. Human Interleukin 24 (IL-24) is a multifunctional cytokine that associates with cell membrane receptors and plays critical roles in oncogenesis, immune response, host defense and tissue homeostasis. Since the optical control of PPI is advantageous over other approaches, particularly in terms of temporal and spatial resolution, we have developed a strategy based on genetic code expansion technology for the OFF-to-ON switch of the binding between IL-24 and one of its receptors, IL-20R2, by light. Introduction of the photocaged non-canonical amino acid ortho-nitrobenzyl tyrosine at selected positions of IL-20R2 largely inhibits heterocomplex formation as determined by microscale thermophoresis and yeast display. Irradiation with UV light (365 nm), which removes the caging group and reconstitutes the canonical tyrosines, restores the native binding strength between IL-24 and IL-20R2. We envision that photocaged IL-20R2 may become a useful tool for the photo-control of the JAK/STAT signalling cascade.
This research was funded by Czech Academy of Sciences, grant RVO 86652036.