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Since the determination of the first molecular models of proteins there has been interest in creating proteins artificially, but such methods have only become widely successful in the last decade. Gradual improvements over a long period of time have now yielded numerous examples of non-natural proteins, many of which are built from repeated elements. In this review we discuss the design of such symmetrical proteins and their various applications in chemistry and medicine.

Recently an artificial protein named Pizza6 was reported, which possesses six identical tandem repeats and adopts a monomeric β-propeller fold with sixfold structural symmetry. Pizza2, a truncated form that consists of a double tandem repeat, self-assembles into a trimer reconstructing the same propeller architecture as Pizza6. The ability of pizza proteins to self-assemble to form complete propellers makes them interesting building blocks to engineer larger symmetrical protein complexes such as symmetric nanoparticles. Here we have explored the self-assembly of Pizza2 fused to homo-oligomerizing peptides. In total, we engineered five different fusion proteins, of which three appeared to assemble successfully into larger complexes. Further characterization of these proteins showed one monodisperse designer protein with a structure close to the intended design. This protein was further fused to eGFP to investigate functionalization of the nanoparticle. The fusion protein was stable and could be expressed in high yield, showing that Pizza-based nanoparticles may be further decorated with functional domains