How To Cycle Protein Conformations With Light

A grand challenge in synthetic biology is to build de novo protein nanomachines. However, a component all nanomachines require, not yet designed in a de novo protein, is a motor that converts biochemical energy into the mechanical work needed to coordinate its activity.

The Baker lab recently published a series of de novo “hinge” proteins that irreversibly switch between two defined conformations upon addition of a binding partner. We have designed these hinges into light-driven protein motor domains that can rapidly cycle back and forth between their two conformational states by crosslinking them to the photoswitchable small molecule azobenzene. We can modulate the cycling behaviour of our motor domains by redesigning their shape changes and/or affinities for their binding partners. We have also designed motor domains that interact with bioactive binding partners, such as the pro-apoptotic peptide BIM-BH3 whose binding and release we can cycle to trigger cell death.

Our motor domains are modular components that can be easily fused to other proteins. This has enabled us to utilize our designs for applications ranging from cycling hydrogel stiffness to controlling protein localization on a surface, and will enable their ready incorporation into future nanomachine designs.