Design of light- and chemically responsive protein assemblies through host-guest interactions

Host-guest (HG) interactions have been widely used to build responsive materials and molecular machines owing to their inherently dynamic nature, interaction specificity, and responsiveness to diverse stimuli. Here, we have set out to exploit these advantages of HG chemistry in the design of dynamic protein assemblies, using a C₄ symmetric protein, ^C98RhuA, as a building block. We show that a ^C98RhuA variant individually modified with β-cyclodextrin (βCD) (host) or azobenzene (guest) functionalities can specifically pair with each other to form highly ordered 1D and 2D assemblies. Association and dissociation of ^βCDRhuA-^azoRhuA assemblies can be controlled by UV and visible light as well as by small-molecule modulators of βCD-azobenzene interactions. Kinetics analyses reveal that ^βCDRhuA-^azoRhuA nanotubes assemble without a nucleation barrier, a highly unusual occurrence for helical supramolecular systems. Taken together, our findings provide a compelling example for achieving complex structural and dynamic outcomes in protein assembly through simple chemical design.