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PDBsum entry 1r8h
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Transcription, replication
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PDB id
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1r8h
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Comparison of the structure and DNA-Binding properties of the e2 proteins from an oncogenic and a non-Oncogenic human papillomavirus.
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Authors
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G.Dell,
K.W.Wilkinson,
R.Tranter,
J.Parish,
R.Leo brady,
K.Gaston.
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Ref.
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J Mol Biol, 2003,
334,
979-991.
[DOI no: ]
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PubMed id
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Abstract
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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.
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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.
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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.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2003,
334,
979-991)
copyright 2003.
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