CRYSTAL-STRUCTURE OF THE DNA-BINDING DOMAIN OF THE EPSTEIN-BARR-VIRUSORIGIN-BINDING PROTEIN, EBNA1, BOUND TO DNA

The Epstein-Barr virus nuclear antigen 1 (EBNA1) protein binds to and activates DNA replication from oriP, the latent origin of DNA replicat ion in Epstein-Barr virus. The crystal structure of the DNA-binding do main of EBNA1 bound to an 18 bp binding site was solved at 2.4 Angstro m resolution. EBNA1 comprises two domains, a flanking and a core domai n. The flanking domain, which includes a helix that projects into the major groove and an extended chain that travels along the minor groove , makes all of the sequence-determining contacts with the DNA. The cor e domain, which is structurally homologous to the complete DNA-binding domain of the bovine papilloma virus E2 protein, makes no direct cont acts with the DNA bases. A model for origin unwinding is proposed that incorporates the known biochemical and structural features of the EBN A1-origin interaction.