The HPV16 E7 viral oncoprotein self-assembles into defined spherical oligomers.

ALONSO, G., GARCÍA-ALAI, M., SMAL, C., CENTENO-CROWLEY, J.M., IACONO, R., CASTAÑO, E., GUALFETTI, P., AND PRAT-GAY, G. DE

BIOCHEMISTRY

Año: 2004 vol. 43 p. 3310 - 3317

0006-2960

The HPV16 E7 Viral Oncoprotein Self-Assembles into Defined Spherical Oligomers† Leonardo G. Alonso,‡ Maria M. García-Alai,‡ Clara Smal,‡ Juan M. Centeno,‡ Rubén Iacono,§ Eduardo Castaño,§ Peter Gualfetti,| and Gonzalo de Prat-Gay*,‡ Instituto Leloir, Facultad de Ciencias Exactas y Naturales, UniVersidad de Buenos Aires, Patricias Argentinas 435, (1405) Buenos Aires, Argentina, Departamento de Quimica Biologica, Facultad de Farmacia y Bioquimica, Universidad de Buenos Aires, Junin 956, C1113AAD, Buenos Aires, Argentina, and Genencor International, Inc., 925 Page Mill Road, Palo Alto, California 94304 Received NoVember 13, 2003; Revised Manuscript Received January 15, 2004 ABSTRACT: Despite the fact that E7 is a major transforming oncoprotein in papillomavirus, its structure and precise molecular mechanism of action remain puzzling to date. E7 proteins share sequence homology and proteasome targeting properties of tumor suppressors with adenovirus E1A and SV40 T antigen, two other paradigmatic oncoproteins from DNA tumor viruses. High-risk HPV16 E7, a nonglobular dimer with some properties of intrinsically disordered proteins, is capable of undergoing pH-dependent conformational transitions that expose hydrophobic surfaces to the solvent. We found that treatment with a chelating agent produced a protein that can readily assemble into homogeneous spherical particles with an average molecular mass of 790 kDa and a diameter of 50 nm, as determined from dynamic light scattering and electron microscopy. The protein undergoes a substantial conformational transition from coil to