Sulfolobus spindle viruses, or Fuselloviridae, are ubiquitous crenarchaeal viruses found in high temperature acidic hot springs around the world (pH = 4.0, T = 70°C), and are especially prevalent in Yellowstone National Park. Because they are relatively easy to isolate, they represent the best studied of the crenarchaeal viruses. This is particularly true for the type virus, Sulfolobus spindle virus one (SSV1). SSV1 contains a double-stranded DNA genome of 15.5 kb, encoding 34 putative open reading frames (ORFs). Interestingly, the genome shows little sequence similarity to organisms other than its SSV homologues. Previous to our work, the limited sequence similarity combined with biochemical analysis had suggested functions for only five of the 34 putative ORFs. Thus, despite its position as the best-studied crenarchaeal virus, functions for most (29) of the SSV1 ORFs remain unknown. In an effort to assign functions to these proteins, we have undertaken biochemical and structural studies of the SSV1 proteome. We have completed structures for two of these proteins. In both cases, the structures reveal well-known folds. This suggests that the lack of sequence similarity in the SSV1 genome is not generally indicative of novel protein folds or functions. Rather, it is indicative of significant evolutionary distance between members of the SSV1 proteome and their homologues in the protein databases. Further, the use of structural homology and the analysis of conserved surface properties suggest functions for both of these SSV1 proteins. This demonstrates the general utility of structural studies on proteins of unknown function; specifically, that structure can predict function.