There is a growing interest in engineering proteins whose function can be controlled with the spatial and temporal precision of light. Here, I present a novel example of a functional light-triggered switch in the calcium-dependent cell-cell adhesion protein E-cadherin, created using a mechanism-based design strategy. I report an 18-fold change in apparent calcium binding affinity upon illumination. This work includes a detailed description of the design methodology used, as well as a detailed examination of functional switching via linked changes in Ca2+ binding and cadherin dimerization. This design opens avenues towards controllable tools that could be applied to many long-standing questions about cadherin's biological function in cell-cell adhesion and downstream signaling. It also presents a potential generalizable strategy for creating additional photoswitchable proteins.
