Elsevier

Virology

Volume 358, Issue 1, 5 February 2007, Pages 10-17
Virology

Rapid Communication
Amino acid substitutions that specifically impair the transcriptional activity of papillomavirus E2 affect binding to the long isoform of Brd4

https://doi.org/10.1016/j.virol.2006.08.035Get rights and content
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Abstract

The E2 protein of papillomaviruses binds to specific sites in the viral genome to regulate its transcription, replication and segregation in mitosis. Amino acid substitutions in the transactivation domain (TAD) of E2, of Arg37 and Ile73, have been shown previously to impair the transcriptional activity of the protein but not its ability to support viral DNA replication. To understand the biochemical basis of this defect, we have used the TADs of a low-risk (HPV11) and a high-risk (HPV31) human papillomavirus (HPV) as affinity ligands to capture proteins from whole cell extracts that can associate with these domains. The major TAD-binding protein was identified by mass spectrometry and western blotting as the long isoform of Brd4. Binding to Brd4 was also demonstrated for the E2 TADs of other papillomaviruses including cutaneous and animal types. For HPV11, HPV31 and CRPV E2, we found that binding to Brd4 is significantly reduced by substitutions of Arg37 and Ile73. Since these amino acids are located near each other in the 3-dimensional structure of the TAD, we suggest that they define a conserved surface involved in binding Brd4 to regulate viral gene transcription.

Keywords

Papillomavirus
E2
Brd4
Bromodomain-containing protein 4
Transcription
Protein–protein interaction
Viral–host interaction

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