Design of a photoswitchable cadherin.
There is a growing interest in engineering proteins whose function can be controlled with the spatial and temporal precision of light. Here, we present a novel example of a functional light-triggered switch in the Ca-dependent cell-cell adhesion protein E-cadherin, created using a mechanism-based design strategy. We report an 18-fold change in apparent Ca(2+) binding affinity upon illumination. Our results include a detailed examination of functional switching via linked changes in Ca(2+) binding and cadherin dimerization. This design opens avenues toward controllable tools that could be applied to many long-standing questions about cadherin's biological function in cell-cell adhesion and downstream signaling.
Graduate Group in Biophysics, University of California, San Francisco, San Francisco, California 94158, USA. ryan.ritterson@cal.berkeley.edu
Ryan S
RS
Ritterson
Kristopher M
KM
Kuchenbecker
Michael
M
Michalik
Tanja
T
Kortemme
D015820:Cadherins / Q000737:chemistry / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion; D019281:Dimerization; D008958:Models, Molecular; D015394:Molecular Structure; D055668:Photochemical Processes; D015202:Protein Engineering
D015820:Cadherins; D002118:Calcium