Sequence Evolution of the Intrinsically Disordered and Globular Domains of a Model Viral Oncoprotein

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In the present work, we have used the papillomavirus E7 oncoprotein to pursue structure-function and evolutionary studies that take into account intrinsic disorder and the conformational diversity of globular domains. The intrinsically disordered (E7N) and globular (E7C) domains of E7 show similar d...

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Autores principales: Chemes, L.B., Glavina, J., Alonso, L.G., Marino-Buslje, C., de Prat-Gay, G., Sánchez, I.E.
Formato: Artículo publishedVersion
Lenguaje:Inglés
Publicado: 2012
Materias:
cysteine
protein E7
zinc
article
binding site
coevolution
dimerization
molecular evolution
nonhuman
oxidation reduction reaction
Papilloma virus
peptide mapping
protein analysis
protein conformation
protein domain
protein function
protein motif
protein structure
sequence alignment
sequence analysis
structural homology
structure activity relation
Amino Acid Motifs
Amino Acid Sequence
Binding Sites
Dimerization
Evolution, Molecular
Humans
Papillomavirus E7 Proteins
Protein Conformation
Protein Structure, Tertiary
Sequence Alignment
Structure-Activity Relationship
Zinc
Papillomaviridae
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_19326203_v7_n10_p_Chemes
Aporte de:
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
id paperaa:paper_19326203_v7_n10_p_Chemes
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spelling paperaa:paper_19326203_v7_n10_p_Chemes2023-06-12T16:51:31Z Sequence Evolution of the Intrinsically Disordered and Globular Domains of a Model Viral Oncoprotein PLoS ONE 2012;7(10) Chemes, L.B. Glavina, J. Alonso, L.G. Marino-Buslje, C. de Prat-Gay, G. Sánchez, I.E. cysteine protein E7 zinc article binding site coevolution dimerization molecular evolution nonhuman oxidation reduction reaction Papilloma virus peptide mapping protein analysis protein conformation protein domain protein function protein motif protein structure sequence alignment sequence analysis structural homology structure activity relation Amino Acid Motifs Amino Acid Sequence Binding Sites Dimerization Evolution, Molecular Humans Papillomavirus E7 Proteins Protein Conformation Protein Structure, Tertiary Sequence Alignment Structure-Activity Relationship Zinc Papillomaviridae In the present work, we have used the papillomavirus E7 oncoprotein to pursue structure-function and evolutionary studies that take into account intrinsic disorder and the conformational diversity of globular domains. The intrinsically disordered (E7N) and globular (E7C) domains of E7 show similar degrees of conservation and co-evolution. We found that E7N can be described in terms of conserved and coevolving linear motifs separated by variable linkers, while sequence evolution of E7C is compatible with the known homodimeric structure yet suggests other activities for the domain. Within E7N, inter-residue relationships such as residue co-evolution and restricted intermotif distances map functional coupling and co-occurrence of linear motifs that evolve in a coordinate manner. Within E7C, additional cysteine residues proximal to the zinc-binding site may allow redox regulation of E7 function. Moreover, we describe a conserved binding site for disordered domains on the surface of E7C and suggest a putative target linear motif. Both homodimerization and peptide binding activities of E7C are also present in the distantly related host PHD domains, showing that these two proteins share not only structural homology but also functional similarities, and strengthening the view that they evolved from a common ancestor. Finally, we integrate the multiple activities and conformations of E7 into a hierarchy of structure-function relationships. © 2012 Chemes et al. Fil:Chemes, L.B. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Alonso, L.G. 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. 2012 info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion application/pdf eng info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_19326203_v7_n10_p_Chemes
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-134
collection Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
language Inglés
orig_language_str_mv eng
topic cysteine
protein E7
zinc
article
binding site
coevolution
dimerization
molecular evolution
nonhuman
oxidation reduction reaction
Papilloma virus
peptide mapping
protein analysis
protein conformation
protein domain
protein function
protein motif
protein structure
sequence alignment
sequence analysis
structural homology
structure activity relation
Amino Acid Motifs
Amino Acid Sequence
Binding Sites
Dimerization
Evolution, Molecular
Humans
Papillomavirus E7 Proteins
Protein Conformation
Protein Structure, Tertiary
Sequence Alignment
Structure-Activity Relationship
Zinc
Papillomaviridae
spellingShingle cysteine
protein E7
zinc
article
binding site
coevolution
dimerization
molecular evolution
nonhuman
oxidation reduction reaction
Papilloma virus
peptide mapping
protein analysis
protein conformation
protein domain
protein function
protein motif
protein structure
sequence alignment
sequence analysis
structural homology
structure activity relation
Amino Acid Motifs
Amino Acid Sequence
Binding Sites
Dimerization
Evolution, Molecular
Humans
Papillomavirus E7 Proteins
Protein Conformation
Protein Structure, Tertiary
Sequence Alignment
Structure-Activity Relationship
Zinc
Papillomaviridae
Chemes, L.B.
Glavina, J.
Alonso, L.G.
Marino-Buslje, C.
de Prat-Gay, G.
Sánchez, I.E.
Sequence Evolution of the Intrinsically Disordered and Globular Domains of a Model Viral Oncoprotein
topic_facet cysteine
protein E7
zinc
article
binding site
coevolution
dimerization
molecular evolution
nonhuman
oxidation reduction reaction
Papilloma virus
peptide mapping
protein analysis
protein conformation
protein domain
protein function
protein motif
protein structure
sequence alignment
sequence analysis
structural homology
structure activity relation
Amino Acid Motifs
Amino Acid Sequence
Binding Sites
Dimerization
Evolution, Molecular
Humans
Papillomavirus E7 Proteins
Protein Conformation
Protein Structure, Tertiary
Sequence Alignment
Structure-Activity Relationship
Zinc
Papillomaviridae
description In the present work, we have used the papillomavirus E7 oncoprotein to pursue structure-function and evolutionary studies that take into account intrinsic disorder and the conformational diversity of globular domains. The intrinsically disordered (E7N) and globular (E7C) domains of E7 show similar degrees of conservation and co-evolution. We found that E7N can be described in terms of conserved and coevolving linear motifs separated by variable linkers, while sequence evolution of E7C is compatible with the known homodimeric structure yet suggests other activities for the domain. Within E7N, inter-residue relationships such as residue co-evolution and restricted intermotif distances map functional coupling and co-occurrence of linear motifs that evolve in a coordinate manner. Within E7C, additional cysteine residues proximal to the zinc-binding site may allow redox regulation of E7 function. Moreover, we describe a conserved binding site for disordered domains on the surface of E7C and suggest a putative target linear motif. Both homodimerization and peptide binding activities of E7C are also present in the distantly related host PHD domains, showing that these two proteins share not only structural homology but also functional similarities, and strengthening the view that they evolved from a common ancestor. Finally, we integrate the multiple activities and conformations of E7 into a hierarchy of structure-function relationships. © 2012 Chemes et al.
format Artículo
Artículo
publishedVersion
author Chemes, L.B.
Glavina, J.
Alonso, L.G.
Marino-Buslje, C.
de Prat-Gay, G.
Sánchez, I.E.
author_facet Chemes, L.B.
Glavina, J.
Alonso, L.G.
Marino-Buslje, C.
de Prat-Gay, G.
Sánchez, I.E.
author_sort Chemes, L.B.
title Sequence Evolution of the Intrinsically Disordered and Globular Domains of a Model Viral Oncoprotein
title_short Sequence Evolution of the Intrinsically Disordered and Globular Domains of a Model Viral Oncoprotein
title_full Sequence Evolution of the Intrinsically Disordered and Globular Domains of a Model Viral Oncoprotein
title_fullStr Sequence Evolution of the Intrinsically Disordered and Globular Domains of a Model Viral Oncoprotein
title_full_unstemmed Sequence Evolution of the Intrinsically Disordered and Globular Domains of a Model Viral Oncoprotein
title_sort sequence evolution of the intrinsically disordered and globular domains of a model viral oncoprotein
publishDate 2012
url http://hdl.handle.net/20.500.12110/paper_19326203_v7_n10_p_Chemes
work_keys_str_mv AT chemeslb sequenceevolutionoftheintrinsicallydisorderedandglobulardomainsofamodelviraloncoprotein
AT glavinaj sequenceevolutionoftheintrinsicallydisorderedandglobulardomainsofamodelviraloncoprotein
AT alonsolg sequenceevolutionoftheintrinsicallydisorderedandglobulardomainsofamodelviraloncoprotein
AT marinobusljec sequenceevolutionoftheintrinsicallydisorderedandglobulardomainsofamodelviraloncoprotein
AT depratgayg sequenceevolutionoftheintrinsicallydisorderedandglobulardomainsofamodelviraloncoprotein
AT sanchezie sequenceevolutionoftheintrinsicallydisorderedandglobulardomainsofamodelviraloncoprotein
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