Self-assembled proteins hold tremendous promise for creating a range of useful templates on the nano- to microscale. In addition to advantages of self-assembly in aqueous environments, proteins can easily be functionalized through standard genetic engineering techniques, enabling incorporation of new chemistries, allowing gene fusions with existing enzymes, or incorporating peptides for nucleating a diverse range of inorganic materials. In particular, proteins from extremophiles have the potential to extend practical applications of proteins well beyond the environmental limits of conventional biotechnology. Extremophilic chaperones are particularly promising because of their restorative functions within the cell and their ability to facilitate protein folding under harsh conditions.

We have recently discovered a new type of filamentous protein (the γ prefoldin, or γ-PFD) from the hyperthermophile Methanocaldococcus jannaschii. The filaments are polydisperse in length (microns) and monodisperse in width (8.5 nm) and height (4 nm). They are also remarkably stable, maintaining their structure up to at least 100ºC and in 7 M guanidinium chloride. With the overall aim of utilizing γ-PFD filaments as structural components in 3-D nano-scale architectures, we describe here the kinetic scheme behind γ-PFD filament formation and demonstrate control over filament length by rational design of an extension resistance mutant protein (so-called TERMs, or thermophilic extension resistant mutants). We then demonstrate self-assembly of this filament with functionalized ends and a different functionalized interior. The next phase of this project involves using powerful genetic selection methodology to create periodic 3-D architectures of arbitrary geometry, and progress toward this end will be discussed.