Structure of the papillomavirus DNA-tethering complex E2:Brd4 and a peptide that ablates HPV chromosomal association.

Many DNA viruses that are latent in dividing cells are noncovalent passengers on mitotic chromosomes and require specific viral-encoded and cellular factors for this activity. The chromosomal protein Brd4 is implicated in the hitchhiking of bovine papillomavirus-1 (BPV-1), and the viral protein E2 binds to both plasmids and Brd4. Here, we present the X-ray crystal structure of the carboxy-terminal domain of Brd4 in complex with HPV-16 E2, and with this information have developed a Brd4-Tat fusion protein that is efficiently taken up by different transformed cells harboring HPV plasmids.

The X-ray structure of the papillomavirus helicase in complex with its molecular matchmaker E2.

DNA replication of the papillomaviruses is specified by cooperative binding of two proteins to the ori site: the enhancer E2 and the viral initiator E1, a distant member of the AAA+ family of proteins. Formation of this prereplication complex is an essential step toward the construction of a functional, multimeric E1 helicase and DNA melting. To understand how E2 interacts with E1 to regulate this process, we have solved the X-ray structure of a complex containing the HPV18 E2 activation domain bound to the helicase domain of E1.