The conserved core enzymatic activities and the distinct dynamics of polyomavirus large T antigens.
Several human polyomaviruses including JCV, BKV and TSV are associated with diseases, particularly in immunosuppressed patients. While the large T antigen (LT) encoded by the monkey polyomavirus SV40 is well studied, and possesses intrinsic ATPase and DNA helicase activities, the LTs of the human polyomaviruses are relatively uncharacterized. In order to evaluate whether these enzymatic activities, which are required for viral DNA replication, are conserved between polyomaviruses, we performed a comparative study using the LTs from JCV, TSV and SV40. The ATPase and DNA helicase activities and the interaction with the cellular tumor suppressor p53 were assayed for the purified Zn-ATPase domains of the three LTs. We found that all Zn-ATPases were active ATPases. The Zn-ATPase domains also functioned as DNA helicases, although the measured kinetic constants differed among the three proteins. In addition, when tested against four small molecule ATPase inhibitors, the Zn-ATPase domains of TSV was more resistant than that of SV40 and JCV. Our results show that, while LTs from JCV and TSV share the core ATPase and DNA helicase activities, they possess important functional differences that might translate into their respective abilities to infect and replicate in hosts.
Department of Biological Sciences, University of Pittsburgh, 4249 Fifth Avenue, Pittsburgh, PA 15260, USA.
Ping
P
An
Department of Biological Sciences, University of Pittsburgh, 4249 Fifth Avenue, Pittsburgh, PA 15260, USA.
Jeffrey L
JL
Brodsky
Department of Biological Sciences, University of Pittsburgh, 4249 Fifth Avenue, Pittsburgh, PA 15260, USA. Electronic address: pipas@pitt.edu.
James M
JM
Pipas
D000251:Adenosine Triphosphatases / Q000737:chemistry*; D000595:Amino Acid Sequence; D000957:Antigens, Viral, Tumor / Q000737:chemistry*; D004265:DNA Helicases / Q000737:chemistry*; D007577:JC Virus / Q000201:enzymology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011120:Polyomavirus / Q000201:enzymology*; D017434:Protein Structure, Tertiary; D013539:Simian virus 40 / Q000201:enzymology
D000957:Antigens, Viral, Tumor; D000251:Adenosine Triphosphatases; D004265:DNA Helicases
ATPase; DNA helicase; Polyomavirus; Protein–protein interaction; p53