Papillomaviral infection causes both benign and malignant lesions and is a
necessary cause of cervical carcinoma. Replication of this virus requires the
replication initiation proteins E1 and E2, which bind cooperatively at the
origin of replication (ori) as an (E1)2-(E2)2-DNA complex. This is a precursor
to larger E1 complexes that distort and unwind the ori. We present the crystal
structure of the E1 DNA binding domain refined to 1.9 A resolution. Residues
critical for DNA binding are located on an extended loop and an alpha helix. We
identify the E1 dimerization surface by selective mutations at an E1/E1
interface observed in the crystal and propose a model for the (E1)2-DNA complex.
These and other observations suggest how the E1 DNA binding domain orchestrates
assembly of the hexameric helicase on the ori.
