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

Biochemistry. 1999 Dec 7;38(49):16115-24. doi: 10.1021/bi991633x.

Abstract

Papillomaviral E2 proteins participate in viral DNA replication and transcriptional regulation. We have solved the solution structure of the DNA-binding domain of the E2 protein from bovine papillomavirus (BPV-1). The structure 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) spectroscopic data. The root-mean-square deviation for structured regions of the monomer when superimposed to the average is 0.73 +/- 0.10 A for backbone atoms and 1.42 +/- 0.16 A for heavy atoms. The 101 residue construct used in this study (residues 310-410) is about 4.5 kcal/mol more stable than a minimal domain comprising the C-terminal 85 amino acid residues (residues 326-410). The structure of the core domain contained within BPV-1 E2 is similar to the corresponding regions of other papilloma viral 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 the minimal domain.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bovine papillomavirus 1 / chemistry*
  • Cattle
  • Crystallography, X-Ray
  • DNA, Viral / chemistry
  • DNA, Viral / metabolism*
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / metabolism
  • Models, Molecular
  • Nuclear Magnetic Resonance, Biomolecular
  • Peptide Fragments / chemistry*
  • Peptide Fragments / metabolism
  • Protein Denaturation
  • Protein Folding
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Solutions
  • Structure-Activity Relationship
  • Thermodynamics
  • Urea
  • Viral Proteins / chemistry*
  • Viral Proteins / metabolism

Substances

  • DNA, Viral
  • DNA-Binding Proteins
  • E2 protein, Bovine papillomavirus
  • Peptide Fragments
  • Solutions
  • Viral Proteins
  • Urea

Associated data

  • PDB/1DBD