A model for polyomavirus helicase activity derived in part from the AlphaFold2 structure of SV40 T-antigen

Enzymes termed helicases are essential for the replication of DNA tumor viruses. Unfortunately, much remains to be determined about this class of enzymes, including their structures and the mechanism(s) they employ to unwind DNA. Herein, we present the full-length structure of a model helicase encoded by a DNA tumor virus. Moreover, this AI-based structure has been analyzed in terms of its basic functional properties, such as the orientation of the helicase at replication forks and the relative locations of the amino acid residues that are critical for helicase activity. Obtaining this information is important because it permits proposals regarding how DNA is routed through these model helicases. Also presented is structural evidence that the conclusions drawn from our detailed analyses of one model helicase, encoded by one class of tumor viruses, are likely to apply to other viral and eukaryotic helicases.