Materials scientists increasingly draw inspiration from the study of how biological systems fabricate materials under mild synthetic conditions by using self‐assembled macromolecular templates. Containerlike protein architectures such as viral capsids and ferritin are examples of such biological templates. These protein cages have three distinct interfaces that can be synthetically exploited: the interior, the exterior, and the interface between subunits. The subunits that comprise the building blocks of these structures can be modified both chemically and genetically in order to impart designed functionality to different surfaces of the cage. Therefore, the cages possess a great deal of synthetic flexibility, which allows for the introduction of multifunctionality in a single cage. In addition, hierarchical assembly of the functionalized cages paves the way for development of a new class of materials with a wide range of applications from electronics to biomedicine.

Of the three domains of life (Eukarya, Bacteria, and Archaea), the least understood is Archaea and its associated viruses. Many Archaea are extremophiles, with species that are capable of growth at some of the highest temperatures and extremes of pH of all known organisms. Phylogenetic rRNA-encoding DNA analysis places many of the hyperthermophilic Archaea (species with an optimum growth >80°C) at the base of the universal tree of life, suggesting that thermophiles were among the first forms of life on earth. Very few viruses have been identified from Archaea as compared to Bacteria and Eukarya. We report here the structure of a hyperthermophilic virus isolated from an archaeal host found in hot springs in Yellowstone National Park. The sequence of the circular double-stranded DNA viral genome shows that it shares little similarity to other known genes in viruses or other organisms. By comparing the tertiary and quaternary structures of the coat protein of this virus with those of a bacterial and an animal virus, we find conformational relationships among all three, suggesting that some viruses may have a common ancestor that precedes the division into three domains of life >3 billion years ago.

Here we present generalized methods for chemically modifying the surface of a viral protein cage; this exploits the chemistry of native and engineered surface exposed functional groups for multivalent presentation of ligands.