Structural code for DNA recognition revealed in crystal structures of papillomavirus E2-DNA targets

Transcriptional regulation in papillomaviruses depends on sequence-specific binding of the regulatory protein E2 to several sites in the viral genome. Crystal structures of bovine papillomavirus E2 DNA targets reveal a confor mational variant of B-DNA characterized by a roll-induced writhe and helica l repeat of 10.5 bp per turn. A comparison between the free and the protein -bound DNA demonstrates that the intrinsic structure of the DNA regions con tacted directly by the protein and the deformability of the DNA region that is not contacted by the protein are critical for sequence-specific protein /DNA recognition and hence for gene-regulatory signals in the viral system. We show that the selection of dinucleotide or longer segments with appropr iate conformational characteristics, when positioned at correct intervals a long the DNA helix, can constitute a structural code for DNA recognition by regulatory proteins. This structural code facilitates the formation of a c omplementary protein-DNA interface that can be further specified by hydroge n bonds and nonpolar interactions between the protein amino acids and the D NA bases.