The HPV16 E7 Viral Oncoprotein Self-Assembles into Defined Spherical Oligomers
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 ot...
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todo:paper_00062960_v43_n12_p3310_Alonso2023-10-03T14:04:23Z The HPV16 E7 Viral Oncoprotein Self-Assembles into Defined Spherical Oligomers Alonso, L.G. García-Alai, M.M. Smal, C. Centeno, J.M. Iacono, R. Castaño, E. Gualfetti, P. De Prat-Gay, G. Chelation DNA Hydrophobicity Oligomers pH Proteins Self assembly Tumors Viruses Oncoproteins Spherical materials Biochemistry congo red oligomer oncoprotein protein E7 thioflavine virus protein virus T antigen article beta sheet cancer inhibition circular dichroism conformational transition DNA tumor virus electron microscopy fluorescence hydrophobicity light scattering molecular mechanics molecular weight nonhuman pH measurement priority journal protein assembly protein binding protein conformation protein folding protein stability protein structure protein tertiary structure sequence homology Simian virus 40 Wart virus Casein Kinase II Circular Dichroism Congo Red Dimerization Fluorescent Dyes Humans Molecular Weight Oncogene Proteins, Viral Papillomaviridae Phosphorylation Protein Binding Protein Structure, Secondary Protein-Serine-Threonine Kinases Solubility Thiazoles Virus Assembly Zinc Adenoviridae DNA viruses Human papillomavirus types Papillomavirus Simiae Simian virus 40 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 β-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 β-sheet structures similar to those found in amyloids, although no fibrillar or insoluble material was observed under our experimental conditions. Fil:Alonso, L.G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:García-Alai, M.M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Smal, C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:De Prat-Gay, G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00062960_v43_n12_p3310_Alonso |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Chelation DNA Hydrophobicity Oligomers pH Proteins Self assembly Tumors Viruses Oncoproteins Spherical materials Biochemistry congo red oligomer oncoprotein protein E7 thioflavine virus protein virus T antigen article beta sheet cancer inhibition circular dichroism conformational transition DNA tumor virus electron microscopy fluorescence hydrophobicity light scattering molecular mechanics molecular weight nonhuman pH measurement priority journal protein assembly protein binding protein conformation protein folding protein stability protein structure protein tertiary structure sequence homology Simian virus 40 Wart virus Casein Kinase II Circular Dichroism Congo Red Dimerization Fluorescent Dyes Humans Molecular Weight Oncogene Proteins, Viral Papillomaviridae Phosphorylation Protein Binding Protein Structure, Secondary Protein-Serine-Threonine Kinases Solubility Thiazoles Virus Assembly Zinc Adenoviridae DNA viruses Human papillomavirus types Papillomavirus Simiae Simian virus 40 |
| spellingShingle |
Chelation DNA Hydrophobicity Oligomers pH Proteins Self assembly Tumors Viruses Oncoproteins Spherical materials Biochemistry congo red oligomer oncoprotein protein E7 thioflavine virus protein virus T antigen article beta sheet cancer inhibition circular dichroism conformational transition DNA tumor virus electron microscopy fluorescence hydrophobicity light scattering molecular mechanics molecular weight nonhuman pH measurement priority journal protein assembly protein binding protein conformation protein folding protein stability protein structure protein tertiary structure sequence homology Simian virus 40 Wart virus Casein Kinase II Circular Dichroism Congo Red Dimerization Fluorescent Dyes Humans Molecular Weight Oncogene Proteins, Viral Papillomaviridae Phosphorylation Protein Binding Protein Structure, Secondary Protein-Serine-Threonine Kinases Solubility Thiazoles Virus Assembly Zinc Adenoviridae DNA viruses Human papillomavirus types Papillomavirus Simiae Simian virus 40 Alonso, L.G. García-Alai, M.M. Smal, C. Centeno, J.M. Iacono, R. Castaño, E. Gualfetti, P. De Prat-Gay, G. The HPV16 E7 Viral Oncoprotein Self-Assembles into Defined Spherical Oligomers |
| topic_facet |
Chelation DNA Hydrophobicity Oligomers pH Proteins Self assembly Tumors Viruses Oncoproteins Spherical materials Biochemistry congo red oligomer oncoprotein protein E7 thioflavine virus protein virus T antigen article beta sheet cancer inhibition circular dichroism conformational transition DNA tumor virus electron microscopy fluorescence hydrophobicity light scattering molecular mechanics molecular weight nonhuman pH measurement priority journal protein assembly protein binding protein conformation protein folding protein stability protein structure protein tertiary structure sequence homology Simian virus 40 Wart virus Casein Kinase II Circular Dichroism Congo Red Dimerization Fluorescent Dyes Humans Molecular Weight Oncogene Proteins, Viral Papillomaviridae Phosphorylation Protein Binding Protein Structure, Secondary Protein-Serine-Threonine Kinases Solubility Thiazoles Virus Assembly Zinc Adenoviridae DNA viruses Human papillomavirus types Papillomavirus Simiae Simian virus 40 |
| description |
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 β-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 β-sheet structures similar to those found in amyloids, although no fibrillar or insoluble material was observed under our experimental conditions. |
| format |
JOUR |
| author |
Alonso, L.G. García-Alai, M.M. Smal, C. Centeno, J.M. Iacono, R. Castaño, E. Gualfetti, P. De Prat-Gay, G. |
| author_facet |
Alonso, L.G. García-Alai, M.M. Smal, C. Centeno, J.M. Iacono, R. Castaño, E. Gualfetti, P. De Prat-Gay, G. |
| author_sort |
Alonso, L.G. |
| title |
The HPV16 E7 Viral Oncoprotein Self-Assembles into Defined Spherical Oligomers |
| title_short |
The HPV16 E7 Viral Oncoprotein Self-Assembles into Defined Spherical Oligomers |
| title_full |
The HPV16 E7 Viral Oncoprotein Self-Assembles into Defined Spherical Oligomers |
| title_fullStr |
The HPV16 E7 Viral Oncoprotein Self-Assembles into Defined Spherical Oligomers |
| title_full_unstemmed |
The HPV16 E7 Viral Oncoprotein Self-Assembles into Defined Spherical Oligomers |
| title_sort |
hpv16 e7 viral oncoprotein self-assembles into defined spherical oligomers |
| url |
http://hdl.handle.net/20.500.12110/paper_00062960_v43_n12_p3310_Alonso |
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