- Campos, Luis A;
- Sharma, Rajendra;
- Alvira, Sara;
- Ruiz, Federico M;
- Ibarra-Molero, Beatriz;
- Sadqi, Mourad;
- Alfonso, Carlos;
- Rivas, Germán;
- Sanchez-Ruiz, Jose M;
- Romero Garrido, Antonio;
- Valpuesta, José M;
- Muñoz, Victor
The macromolecular machines of life use allosteric control to self-assemble, dissociate and change shape in response to signals. Despite enormous interest, the design of nanoscale allosteric assemblies has proven tremendously challenging. Here we present a proof of concept of allosteric assembly in which an engineered fold switch on the protein monomer triggers or blocks assembly. Our design is based on the hyper-stable, naturally monomeric protein CI2, a paradigm of simple two-state folding, and the toroidal arrangement with 6-fold symmetry that it only adopts in crystalline form. We engineer CI2 to enable a switch between the native and an alternate, latent fold that self-assembles onto hexagonal toroidal particles by exposing a favorable inter-monomer interface. The assembly is controlled on demand via the competing effects of temperature and a designed short peptide. These findings unveil a remarkable potential for structural metamorphosis in proteins and demonstrate key principles for engineering protein-based nanomachinery.