A highly controllable protein self-assembly system with morphological versatility induced by reengineered host-guest interactions.

Manipulating proteins to self-assemble into highly ordered nanostructures not only provides insights into the natural protein assembly process but also allows access to advanced biomaterials. Host-guest interactions have been widely used in the construction of artificial protein assemblies in recent years. CB[8] can selectively associate with two tripeptide Phe-Gly-Gly (FGG) tags with an extraordinarily high binding affinity (Kter = 1.5 × 1011 M-2 ). However, the FGG tags utilized before are all fixed to the N-termini via genetic fusion; this spatial limitation greatly confined the availability of the CB[8]/FGG pair in the construction of more sophisticated protein nanostructures. Here we first designed and synthesized a maleimide-functionalized Phe-Gly-Gly tag as a versatile site-specific protein modification tool; this designed tag can site-selectively introduce desired guest moieties onto protein surfaces for host-guest driven protein assembly. When regulating the self-assembly process of proteins and CB[8], the constructed protein nanosystem can exhibit distinctive morphological diversities ranging from nanorings, nanospirals, nanowires to superwires. This work developed a new strategy for site-specific protein modification of the CB[8] binding tag and provides a possible direction for the construction of 'smart', dynamic self-assembly systems.