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The HPV16 E7 Viral Oncoprotein Self-Assembles into Defined Spherical Oligomers

Alonso, Leonardo G., García-Alai, Maria M., Smal, Clara, Centeno, Juan M., Iacono, Rubén, Castaño, Eduardo, Gualfetti, Peter, de Prat-Gay, Gonzalo·2004·Biochemistry
DOI 10.1021/bi036037o
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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 beta-sheet structure, with concomitant consolidation of tertiary structure as judged by circular dichroism and fluorescence. The assembly process is very slow, in agreement with a substantial energy barrier caused by structural rearrangements. The resulting particles are highly stable, cooperatively folded, and capable of binding both Congo Red and thioflavin T, reporters of repetitive beta-sheet structures similar to those found in amyloids, although no fibrillar or insoluble material was observed under our experimental conditions.

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Metadata

Authors
Alonso, L. G., García-Alai, M. M., Smal, C., Centeno, J. M., Iacono, R., Castaño, E., Gualfetti, P., & de Prat-Gay, G.
Affiliations
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
Venue
Biochemistry
Publisher
American Chemical Society (ACS)
Published
2004-03-01
Volume
43
Issue
12
Pages
3310-3317
ISSN
  • 0006-2960
  • 1520-4995
DOI
10.1021/bi036037o
Cited by
52
References
1
Language
en

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CoChat. (2026). Citation check: The HPV16 E7 Viral Oncoprotein Self-Assembles into Defined Spherical Oligomers. https://app.cochat.ai/papers/10.1021/bi036037o
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Alonso, L. G., García-Alai, M. M., Smal, C., Centeno, J. M., Iacono, R., Castaño, E., Gualfetti, P., & de Prat-Gay, G. (2004). The HPV16 E7 Viral Oncoprotein Self-Assembles into Defined Spherical Oligomers. Biochemistry. https://doi.org/10.1021/bi036037o