Computational design of a self-assembling symmetrical β-propeller protein

TLDR

The authors designed a six‑blade β‑propeller protein that is highly stable, crystallized in multiple forms, and can be oligomerized via domain swapping to produce complexes with fixed blade numbers. The study presents the first perfectly symmetrical β‑propeller protein, demonstrating rapid, template‑agnostic design that yields highly stable, crystallizable assemblies with potential broad bionanotechnology applications.

Abstract

Significance In this study, we have designed and experimentally validated, to our knowledge, the first perfectly symmetrical β-propeller protein. Our results provide insight not only into protein evolution through duplication events, but also into methods for creating designer proteins that self-assemble according to simple arithmetical rules. Such proteins may have very wide uses in bionanotechnology. Furthermore our design approach is both rapid and applicable to many different protein templates. Our novel propeller protein consists of six identical domains known as “blades.” Using a variety of biophysical techniques, we show it to be highly stable and report several high-resolution crystal structures of different forms of the protein. Domain swapping allows us to generate related oligomeric forms with fixed numbers of blades per complex.