Indirect readout of DNA sequence by papillomavirus E2 proteins depends upon net cation uptake

Dukagjin M. Blakaj, Chandramohan Kattamuri, Sergei Khrapunov, Rashmi S. Hegde, Michael Brenowitz

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


The papillomavirus E2 proteins bind with high affinity to palindromic DNA sequences consisting of two highly conserved four base-pair sequences flanking a variable "spacer" of identical length (ACCG NNNN CGGT). While intimate contacts are observed between the bound proteins and conserved DNA in the available co-crystal structures, no contact is seen between the proteins and the spacer DNA. The ability of human papillomavirus strain 16 (HPV-16) E2 and bovine papillomavirus strain 1 (BPV-1) E2 to discriminate among binding sites with different spacer sequences is dependent on their sensitivity to the unique conformational and/or dynamic properties of the spacer DNA in a process termed "indirect readout". Differential sequence-specific K+ uptake in low ionic strength solutions lacking Mg2+ is observed upon E2 protein binding to sites containing the AATT, TTAA or ACGT spacer sequences. In contrast, the cation displacement typical of protein-DNA complex formation is observed at high K+ concentrations or in the presence of Mg 2+. These results are interpreted to reflect the sequence-specific stabilization of bent DNA conformations by cations localized within the narrowed minor grooves of the protein-bound DNA and the intrinsic structure and flexibility of the DNA target. Mg2+ differentially affects the binding of the HPV-16 E2 DNA binding domain (HPV16-E2/D) and the BPV-1 E2 DNA binding domain (BPV1-E2/D) to sites bearing different spacer sequences. This study suggests that monovalent and divalent cations contribute to the discrimination of DNA structure and flexibility that could in turn contribute to the specificity with which HPV16-E2/D and BPV1-E2/D mediate DNA replication and gene transcription.

Original languageEnglish (US)
Pages (from-to)224-240
Number of pages17
JournalJournal of Molecular Biology
Issue number1
StatePublished - Apr 21 2006


  • Cations
  • Indirect readout
  • Papillomavirus E2
  • Protein-DNA

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology


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