A structure-guided mutational analysis of simian virus 40 large T antigen: identification of surface residues required for viral replication and transformation.

ABSTRACT: Simian virus 40 large T antigen (TAg) transforms cells in culture and induces tumors in rodents. Genetic studies suggest that TAg interaction with the chaperone hsp70 and tumor suppressors pRb and p53 may not be sufficient to elicit complete transformation of cells. In order to identify additional cellular factors important for transformation, we designed mutations on the solvent-exposed surface of TAg. We hypothesized that surface residues would interact directly with cellular targets and that the mutation of these residues might disrupt this interaction without perturbing TAg's global structure. Using structural data, we identified 61 amino acids on the surface of TAg. Each surface amino acid was changed to an alanine. Furthermore, five patches containing clusters of charged amino acids

SUBMITTER: Ahuja D 

PROVIDER: S-EPMC2738162 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature