Structure of the BPV-1 E2 DNA-binding domain bound to its DNA target.

The dominant transcriptional regulator of papillomaviruses is the E2 protein. In human papillomaviruses, the E2 protein regulates the expression of the E6 and E7 oncogenes. The functions of E2 are mediated subsequent to its specific interaction with a 12 base-pair palindromic DNA target, the E2-BS. Elucidation of the stereochemical basis of DNA target selection by the E2 protein is a key step in understanding transcriptional regulation in these cancer-causing viruses. The crystal structure of the DNA-binding domain of the bovine papillomavirus-1 E2 protein bound to its DNA target reveals a novel DNA-binding and dimerization motif. The protein is a dimeric beta-barrel with alpha helices on the outer surface that function as recognition helices. A complex and interwoven network of hydrogen bonds characterize the specific protein/DNA interface. The DNA is smoothly curved around the E2 beta-barrel and encompasses the recognition helices in successive major grooves.