Structural correlates for enhanced stability in the E2 DNA-binding domain from bovine papillomavirus

Papillomaviral E2 proteins participate in viral DNA replication and transcr iptional regulation. We have solved the solution structure of the DNA-bindi ng domain of the E2 protein from bovine papillomavirus (BPV-1), The structu re calculation used 2222 distance and 158 dihedral angle restraints for the homodimer (202 residues in total), which were derived from homonuclear and heteronuclear multidimensional nuclear magnetic resonance (NMR) spectrosco pic data. The root-mean-square deviation for structured regions of the mono mer when superimposed to the average is 0.73 +/- 0.10 Angstrom for backbone atoms and 1.42 +/- 0.16 Angstrom for heavy atoms. The 101 residue construc t used in this study (residues 310-410) is about 4.5 kcal/mol more stable t han a minimal domain comprising the C-terminal 85 amino acid residues (resi dues 326-410). The structure of the core domain contained within BPV-1 E2 i s similar to the corresponding regions of other papillomaviral E2 proteins. Here, however, the extra N-terminal 16 residues form a flap that covers a cavity at the dimer interface and play a role in DNA binding. Interactions between residues in the N-terminal extension and the core domain correlate with the greater stability of the longer form of the protein relative to th e minimal domain.