title: Crystal structure of the DNA binding domain of the replication initiation protein E1 from papillomavirus.
abstract: 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.
authors.affiliation: W.M. Keck Structural Biology Center, Cold Spring Harbor, New York 11724, USA.
authors.forename: E J
authors.initials: EJ
authors.lastname: Enemark
authors.forename: G
authors.initials: G
authors.lastname: Chen
authors.forename: D E
authors.initials: DE
authors.lastname: Vaughn
authors.forename: A
authors.initials: A
authors.lastname: Stenlund
authors.forename: L
authors.initials: L
authors.lastname: Joshua-Tor
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D052688:Bovine papillomavirus 1 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002417:Cattle; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics; D019281:Dimerization; D005260:Female; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D027383:Papillomaviridae / Q000472:pathogenicity; D030361:Papillomavirus Infections / Q000209:etiology; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D055672:Static Electricity; D014412:Tumor Virus Infections / Q000209:etiology; D002583:Uterine Cervical Neoplasms / Q000209:etiology; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C069814:E1 protein, Bovine papillomavirus; D014764:Viral Proteins