Formation of the complex of bovine papillomavirus E1 and E2 proteins is modulated by E2 phosphorylation and depends upon sequences within the carboxyl terminus of E1.

The 68-kDa bovine papillomavirus (BPV) type 1 replication protein E1 and the 48-kDa transactivator protein E2 form a complex that specifically binds DNA [Mohr, I.J., Clark, R., Sun, S., Androphy, E.J., MacPherson, P. & Botchan, M.R. (1990) Science 250, 1694-1699]. We have confirmed this observation and shown that the E1-E2 complex binds to DNA fragments that contain the BPV plasmid maintenance sequence 1 and a site for the initiation of bidirectional BPV DNA synthesis. The E1 protein was found to bind preferentially to non- or underphosphorylated species of E2, suggesting that the phosphorylation state of E2 modulates the association of the two proteins. Replication-deficient E1 mutants with single amino acid substitutions and deletions in the carboxyl terminus failed to interact with E2, indicating that a region in the E1 carboxyl terminus is required for E1 to interact with E2. Our results suggest that the replication deficiency of some E1 mutants reflects their inability to associate with E2.