title: Evolutionary and biophysical relationships among the papillomavirus E2 proteins.
abstract: Infection by human papillomavirus (HPV) may result in clinical conditions ranging from benign warts to invasive cancer. The HPV E2 protein represses oncoprotein transcription and is required for viral replication. HPV E2 binds to palindromic DNA sequences of highly conserved four base pair sequences flanking an identical length variable 'spacer'. E2 proteins directly contact the conserved but not the spacer DNA. Variation in naturally occurring spacer sequences results in differential protein affinity that is dependent on their sensitivity to the spacer DNA's unique conformational and/or dynamic properties. This article explores the biophysical character of this core viral protein with the goal of identifying characteristics that associated with risk of virally caused malignancy. The amino acid sequence, 3d structure and electrostatic features of the E2 protein DNA binding domain are highly conserved; specific interactions with DNA binding sites have also been conserved. In contrast, the E2 protein's transactivation domain does not have extensive surfaces of highly conserved residues. Rather, regions of high conservation are localized to small surface patches. Implications to cancer biology are discussed.
authors.affiliation: Department of Biochemistry, Albert Einstein College of Medicine,1300 Morris Park Avenue, Bronx NY 10461, USA.
authors.forename: Dukagjin M
authors.initials: DM
authors.lastname: Blakaj
authors.forename: Narcis
authors.initials: N
authors.lastname: Fernandez-Fuentes
authors.forename: Zigui
authors.initials: Z
authors.lastname: Chen
authors.forename: Rashmi
authors.initials: R
authors.lastname: Hegde
authors.forename: Andras
authors.initials: A
authors.lastname: Fiser
authors.forename: Robert D
authors.initials: RD
authors.lastname: Burk
authors.forename: Michael
authors.initials: M
authors.lastname: Brenowitz
mesh_terms: D005075:Biological Evolution; D001703:Biophysics; D027383:Papillomaviridae / Q000235:genetics*; D055672:Static Electricity; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D016159:Tumor Suppressor Protein p53; D014764:Viral Proteins