DMCA
Comparison of the Structure and DNA-binding Properties of the E2 Proteins from an Oncogenic and
BibTeX
@MISC{Papillomavirus_comparisonof,
author = {A Non-oncogenic Human Papillomavirus and Ghislaine Dell and Kay W. Wilkinson and Rebecca Tranter and Joanna Parish and R. Leo Brady and Kevin Gaston},
title = {Comparison of the Structure and DNA-binding Properties of the E2 Proteins from an Oncogenic and},
year = {}
}
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Abstract
Human papillomaviruses (HPVs) that infect the genital tract can be divided into two groups: high-risk HPV types, such as HPV 16 and HPV 18, are associated with cancer, low-risk HPV types, such as HPV 6, are associated with benign warts. In both high-risk and low-risk HPV types, the papillomavirus E2 protein binds to four sites within the viral long con-trol region (LCR) and regulates viral gene expression. Here, we present the crystal structure of the minimal DNA-binding domain (DBD) from the HPV 6 E2 protein. We show that the HPV 6 E2 DBD is structurally more similar to the HPV 18 and bovine papillomavirus type 1 (BPV1) E2 proteins than it is to the HPV 16 E2 protein. Using gel retardation assays, we show that the hierarchy of E2 sites within the HPV 16 and HPV 6 LCRs are different. However, despite these differences in structure and site preference, both the HPV 16 and 6 E2 DBDs recognise an extended version of the consensus E2 binding site derived from studies of the BPV1 E2 protein. In both cases, the preferred binding site is 50 AACCGN4CGGTT 30; where the additional flanking base-pairs are in bold and N4 represents a four base-pair central spacer. Both of these HPV proteins bind preferentially to E2 sites that contain an A:T-rich central spacer. We show that the preference for an A:T-rich central spacer is due, at least in part, to the need to adopt a DNA confor-mation that facilitates protein contacts with the flanking base-pairs.
Keyphrases
e2 protein dna-binding property low-risk hpv type t-rich central spacer additional flanking base-pairs e2 dbd crystal structure papillomavirus type viral gene expression extended version benign wart protein contact e2 dbds genital tract consensus e2 preferred binding site papillomavirus e2 protein base-pair central spacer high-risk hpv type bpv1 e2 protein viral long con-trol region human papillomaviruses minimal dna-binding domain gel retardation assay hpv protein site preference dna confor-mation e2 site
