Functional protein nanostructures: a chemical toolbox

Nature has evolved an optimal synthetic factory in the form of translational and posttranslational processes by which millions of proteins with defined primary sequences and 3D structures can be built. Nature's toolkit gives rise to protein building blocks, which dictates their spatial arrangement to form functional protein nanostructures that serve a myriad of functions in cells, ranging from biocatalysis, formation of structural networks, and regulation of biochemical processes, to sensing. With the advent of chemical tools for site-selective protein modifications and recombinant engineering, there is a rapid development to develop and apply synthetic methods for creating structurally defined, functional protein nanostructures for a broad range of applications in the fields of catalysis, materials and biomedical sciences. In this review, design principles and structural features for achieving and characterizing functional protein nanostructures by synthetic approaches are summarized. The synthetic customization of protein building blocks, the design and introduction of recognition units and linkers and subsequent assembly into structurally defined protein architectures are discussed herein. Key examples of these supramolecular protein nanostructures, their unique functions and resultant impact for biomedical applications are highlighted.