ArticleNucleic acids research2008
Comprehensive comparison of the interaction of the E2 master regulator with its cognate target DNA sites in 73 human papillomavirus types by sequence statistics.
Article in Nucleic acids research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed.
- Review
- E2 protein is the major determinant of specificity at the human papillomavirus origin of replication.PloS one · 2019Article
- Article
- The papillomavirus E2 proteins.Virology · 2013Review
- Identification and analysis of papillomavirus E2 protein binding sites in the human genome.Journal of virology · 2012Article
- The HPV E2-Host Protein-Protein Interactions: A Complex Hijacking of the Cellular Network.The open virology journal · 2012Article
- Large scale genotype comparison of human papillomavirus E2-host interaction networks provides new insights for e2 molecular functions.PLoS pathogens · 2012Article
- Evolutionary variation of papillomavirus E2 protein and E2 binding sites.Virology journal · 2011Article
- Protein flexibility directs DNA recognition by the papillomavirus E2 proteins.Nucleic acids research · 2011Article
- Mutational analysis of kinetic partitioning in protein folding and protein-DNA binding.Protein engineering, design & selection : PEDS · 2011Article
- Replication and transcription of human papillomavirus type 58 genome in Saccharomyces cerevisiae.Virology journal · 2010Article
- Thermodynamics of cooperative DNA recognition at a replication origin and transcription regulatory site.Biochemistry · 2010Article
- Pushing the limits of what is achievable in protein-DNA docking: benchmarking HADDOCK's performance.Nucleic acids research · 2010Article
- Experimental snapshots of a protein-DNA binding landscape.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
- The E8--E2 gene product of human papillomavirus type 16 represses early transcription and replication but is dispensable for viral plasmid persistence in keratinocytes.Journal of virology · 2008Article
- Transition state for protein-DNA recognition.Proceedings of the National Academy of Sciences of the United States of America · 2008Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Mucosal human papillomaviruses (HPVs) are etiological agents of oral, anal and genital cancer. Properties of high- and low-risk HPV types cannot be reduced to discrete molecular traits. The E2 protein regulates viral replication and transcription through a finely tuned interaction with four sites at the upstream regulatory region of the genome. A computational study of the E2-DNA interaction in all 73 types within the alpha papillomavirus genus, including all known mucosal types, indicates that E2 proteins have similar DNA discrimination properties. Differences in E2-DNA interaction among HPV types lie mostly in the target DNA sequence, as opposed to the amino acid sequence of the conserved DNA-binding alpha helix of E2. Sequence logos of natural and in vitro selected sites show an asymmetric pattern of conservation arising from indirect readout, and reveal evolutionary pressure for a putative methylation site. Based on DNA sequences only, we could predict differences in binding energies with a standard deviation of 0.64 kcal/mol. These energies cluster into six discrete affinity hierarchies and uncovered a fifth E2-binding site in the genome of six HPV types. Finally, certain distances between sites, affinity hierarchies and their eventual changes upon methylation, are statistically associated with high-risk types.
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Registered trials
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