Conformational tendencies of the N-terminal domain of the papillomavirus E7 oncoprotein in solution

MARIA M. GARCIA-ALAI; LEONARDO G. ALONSO; G. DE PRAT GAY

Buenos Aires (Argentina)

Congreso; International Biophysics Congress (IUPAB-SAB); 2002

HPV E7 oncoprotein is a natively unfolded protein. Its extended structured conformation at physiological pH facilitates protein-protein  interaction targeting the cellular tumor suppressor retinoblastoma . E7 from high and low risk HPV strains differ mainly in their N-terminal domain . We think that many of the biochemical properties that determine E7s extended tridimentional structure  relay in its N-terminal domain. We constructed a 41 amino acid peptide  of the N-terminal E7 HPV16 for studying  its biophysical behavior in different environments. This peptide presents a random coiled CD spectrum at neutral pH. Known secondary structures can be induced by addition of different solvents. Induction of alpha-helix by TFE or micellar SDS concentrations and Beta-sheet at sub-micellar SDS concentrations show the flexibility of this domain. These transitions seem to be pH dependent  as seen in CD experiments at low and physiological pHs showing that the neutralization of one or some of the acidic residues might be involved. The biophysical characterization of the peptide could explain many of the rare E7 properties and corresponds to the description for the intrinsically unstructured proteins.