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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Autores principales:	Alonso, Leonardo, García Alai, María, Smal, Clara, de Prat Gay, Gonzalo
Publicado:	2004
Materias:	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
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00062960_v43_n12_p3310_Alonso http://hdl.handle.net/20.500.12110/paper_00062960_v43_n12_p3310_Alonso
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paper:paper_00062960_v43_n12_p3310_Alonso
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spelling	paper:paper_00062960_v43_n12_p3310_Alonso2025-07-30T17:13:52Z The HPV16 E7 Viral Oncoprotein Self-Assembles into Defined Spherical Oligomers Alonso, Leonardo García Alai, María Smal, Clara de Prat Gay, Gonzalo 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. 2004 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00062960_v43_n12_p3310_Alonso 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, Leonardo García Alai, María Smal, Clara de Prat Gay, Gonzalo 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.
author	Alonso, Leonardo García Alai, María Smal, Clara de Prat Gay, Gonzalo
author_facet	Alonso, Leonardo García Alai, María Smal, Clara de Prat Gay, Gonzalo
author_sort	Alonso, Leonardo
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
publishDate	2004
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00062960_v43_n12_p3310_Alonso http://hdl.handle.net/20.500.12110/paper_00062960_v43_n12_p3310_Alonso
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The HPV16 E7 Viral Oncoprotein Self-Assembles into Defined Spherical Oligomers

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