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J. Biol. Chem., Vol. 275, Issue 40, 31245-31254, October 6, 2000
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From the Department of Biochemistry and Program in Structural
Biology, New York University Medical Center, Skirball Institute of
Biomolecular Medicine, New York, New York 10016
The papillomavirus E2 proteins regulate the
transcription of all papillomavirus genes and are necessary for viral
DNA replication. Disruption of the E2 gene is commonly associated with
malignancy in cervical carcinoma, indicating that E2 has a role in
regulating tumor progression. Although the E2 proteins from all
characterized papillomaviruses bind specifically to the same 12-base
pair DNA sequence, the cancer-associated human papillomavirus E2
proteins display a unique ability to detect DNA flexibility and
intrinsic curvature. To understand the structural basis for this
phenomenon, we have determined the crystal structures of the human
papillomavirus-18 E2 DNA-binding domain and its complexes with
high and low affinity binding sites. The E2 protein is a dimeric
The atomic coordinates and the structure factors (code 1F9F) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).
The Structural Basis of DNA Target Discrimination by
Papillomavirus E2 Proteins*
-barrel and the E2-DNA interaction is accompanied by a large
deformation of the DNA as it conforms to the E2 surface. DNA
conformation and E2-DNA contacts are similar in both high and low
affinity complexes. The differences in affinity correlate with the
flexibility of the DNA sequence. Preferences of E2 proteins from
different papillomavirus strains for flexible or prebent DNA targets
correlate with the distribution of positive charge on their DNA
interaction surfaces, suggesting a role for electrostatic forces in the
recognition of DNA deformability.
*
This work was supported by Grant CA66964 from the National
Institutes of Health.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Dept. of Biochemistry
and Program in Structural Biology, New York University Medical Center,
Skirball Institute of Biomolecular Medicine, 540 First Ave., New York,
NY 10016. E-mail: rashmi@saturn.med.nyu.edu.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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