PDBsum entry 1r8h

Transcription, replication

PDB id: 1r8h

Contents

Protein chains

(+ 0 more) 87 a.a. *

Ligands

PO4 ×14

Waters ×383

* Residue conservation analysis

PDB id:

1r8h

Name:

Transcription, replication

Title:

Comparison of the structure and DNA binding properties of the e2 proteins from an oncogenic and a non-oncogenic human papillomavirus

Structure:

Regulatory protein e2. Chain: a, b, c, d, e, f. Fragment: DNA-binding domain. Engineered: yes

Source:

Human papillomavirus type 6a. Organism_taxid: 37122. Gene: e2. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Dimer (from PQS)

Resolution:

1.90Å R-factor: 0.195 R-free: 0.258

Authors:

G.Dell,K.W.Wilkinson,R.Tranter,J.Parish,R.L.Brady,K.Gaston

Key ref:

G.Dell et al. (2003). Comparison of the structure and DNA-binding properties of the E2 proteins from an oncogenic and a non-oncogenic human papillomavirus. J Mol Biol, 334, 979-991. PubMed id: 14643661 DOI: 10.1016/j.jmb.2003.10.009

Date:

24-Oct-03 Release date: 23-Dec-03

Protein chains

Q84294  (VE2_HPV6A) -  Regulatory protein E2 from Human papillomavirus type 6a

Seq: 368 a.a.

Struc: 87 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

DOI no: 10.1016/j.jmb.2003.10.009

J Mol Biol 334:979-991 (2003)

PubMed id: 14643661

Comparison of the structure and DNA-binding properties of the E2 proteins from an oncogenic and a non-oncogenic human papillomavirus.

G.Dell, K.W.Wilkinson, R.Tranter, J.Parish, R.Leo Brady, K.Gaston.

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 control 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 5'AACCGN(4)CGGTT3', where the additional flanking base-pairs are in bold and N(4) 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 conformation that facilitates protein contacts with the flanking base-pairs.

Selected figure(s)

Figure 1.
Figure 1. The crystal structure of the HPV 6 E2 DNA-binding domain. (a) Topology of the HPV 6 E2 DBD monomer. (b) Topology of the HPV 6 E2 DBD dimer. The subunits are indicated in red and blue. (c) A comparison of the DBDs from the HPV 6 (blue), HPV 16 (red), and BPV1 (yellow) E2 proteins. The left subunit of each protein is superimposed. (d) A comparison of the b2/b3 loop in the HPV 6 E2 DBD (blue) and BPV1 E2 DBD (yellow). BPV1 E2 Arg370 is indicated in pink. HPV 6 E2 Lys327, Lys323, Asp311 and His366 are indicated in light blue. His366 is present in two conformations in the crystal structure.

Figure 2.
Figure 2. The electrostatic potential energy surface of the E2 DBD. The electrostatic potential energy surfaces of the DBDs from the (a) BPV1, (b) HPV 16, (c) HPV 18, and (d) HPV 6 E2 proteins were calculated using GRASP. Positive potentials are blue, negative potentials are red. The water-probe radius was 1.4 Å and the electrostatic potential is displayed on a scale of -13 k[B]T to +13 k[B]T. (e) The HPV 6 E2 DBD is shown to illustrate the position of the DNA recognition helices in this view.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2003, 334, 979-991) copyright 2003.

Figures were selected by the author.

Author's comment

See also the HPV 6 E2 DBD-DNA complex (2ayg and 2ayb).
K. Gaston