In nature, the most complex tasks performed by the cell—such as nucleic acid and protein synthesis, cargo transport, and ATP production—are accomplished by protein nanomachines. These nanomachines comprise asymmetric assemblies of proteins acting in concert to execute repeated cycles of an ordered series of steps. A component all nanomachines require is a motor that converts biochemical energy into the mechanical motion needed to drive these ordered steps. Previously, the Baker lab has published a series of modular α-helical “hinge” proteins that irreversibly switch between two structurally defined conformations upon addition of a binding partner. Here, we present our research to convert these designs 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 demonstrate how we can modulate the cycling behavior of our motor domains by altering the designed conformational motion and by tuning the properties of binding partners designed to selectively interact with different domain conformations. We also present our progress toward incorporating these motor domains into larger protein assemblies to reversibly cycle between alternate conformations.
Shelley et al. (2026) studied this question.