Binding of the human papillomavirus E1 origin-recognition protein is regulated through complex formation with the E2 enhancer-binding protein

Mark G. Frattini, Laimonis A. Laimins*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

111 Scopus citations

Abstract

The papillomavirus E1 and E2 proteins form heteromeric complexes and individually bind specific sequences within the viral origin of replication. The mechanism by which these proteins are recruited to the origin and the role of the E1/E2 complex in replication remain undefined. To examine the interplay of these replication proteins, we have analyzed the binding of human papillomavirus (HPV) type 31b E1 and E2 proteins to the origin of replication. Binding of E1 to the origin was increased by E2 proteins and required the presence of E2 binding sites. This increase was due to the formation of E1/E2 complexes which preferentially bound E2-responsive sequences, and the magnitude was determined by the relative affinity of the E2 binding sites. While the E1 protein alone bound an A/T-rich sequence at the HPV-31b origin with low affinity, complexes of E1 and E2 bound instead to E2 binding sites with high affinity. The E1/E2 complex bound a similar sequence as E2 homodimers, but only E2 homodimer binding induced a significant increase in hypersensitivity as indicated by DNase I footprinting. In the presence of excess E1, E1 proteins bound both the A/T- etch sequence and E2 binding sites through complex formation with E2. In E2 excess, E1/E2 complexes preferentially formed, and binding was specific for E2 sites. Therefore, changes in the relative amounts of E1 and E2 proteins can dramatically alter the pattern of binding of viral replication factors to the origin. These observations suggest a model whereby modulation of the relative levels of E1 and E2 during the viral life cycle may alter the pattern of origin binding and possibly episomal copy number.

Original languageEnglish (US)
Pages (from-to)12398-12402
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number26
DOIs
StatePublished - Dec 20 1994

ASJC Scopus subject areas

  • General

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