Structural and thermodynamic basis for the enhanced transcriptional control by the human papillomavirus strain-16 E2 protein

Autores
Cicero, Daniel Oscar; Nadra, Alejandro Daniel; Eliseo, Tommaso; Dellarole, Mariano; Paci, Maurizio; de Prat Gay, Gonzalo
Año de publicación
2006
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Strain 16 of the human papillomavirus is responsible for the largest number of cases of cervical cancers linked to this virus, and the E2 protein is the transcriptional regulator of all viral genes. We present the first structure for the DNA binding domain of HPV16 E2 bound to DNA, and in particular, to a natural cognate sequence. The NMR structure of the protein backbone reveals that the overall conformation remains virtually unchanged, and chemical shift analysis of the protein bound to a shorter DNA duplex uncovered a contact out of the minimal E2 DNA binding site, made by lysine 349. This contact was confirmed by duration calorimetry and mutagenesis, with a contribution of 1.0 kcal mol-1 to binding energy. HPV16 E2 has the highest DNA binding affinity and exerts a strict transcriptional control, translated into the repression of the E6 and E7 oncogenes. These novel features provide the structural and thermodynamic basis for this tight transcriptional control, the loss of which correlates with carcinogenesis.
Fil: Cicero, Daniel Oscar. Universita Di Roma; Italia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Nadra, Alejandro Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Eliseo, Tommaso. Universita Di Roma; Italia
Fil: Dellarole, Mariano. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Paci, Maurizio. Universita Di Roma; Italia
Fil: de Prat Gay, Gonzalo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Materia
Human Papillomavirus
Dna Binding Protein
Nmr
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/39171
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Structural and thermodynamic basis for the enhanced transcriptional control by the human papillomavirus strain-16 E2 proteinCicero, Daniel OscarNadra, Alejandro DanielEliseo, TommasoDellarole, MarianoPaci, Mauriziode Prat Gay, GonzaloHuman PapillomavirusDna Binding ProteinNmrhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Strain 16 of the human papillomavirus is responsible for the largest number of cases of cervical cancers linked to this virus, and the E2 protein is the transcriptional regulator of all viral genes. We present the first structure for the DNA binding domain of HPV16 E2 bound to DNA, and in particular, to a natural cognate sequence. The NMR structure of the protein backbone reveals that the overall conformation remains virtually unchanged, and chemical shift analysis of the protein bound to a shorter DNA duplex uncovered a contact out of the minimal E2 DNA binding site, made by lysine 349. This contact was confirmed by duration calorimetry and mutagenesis, with a contribution of 1.0 kcal mol-1 to binding energy. HPV16 E2 has the highest DNA binding affinity and exerts a strict transcriptional control, translated into the repression of the E6 and E7 oncogenes. These novel features provide the structural and thermodynamic basis for this tight transcriptional control, the loss of which correlates with carcinogenesis.Fil: Cicero, Daniel Oscar. Universita Di Roma; Italia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Nadra, Alejandro Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Eliseo, Tommaso. Universita Di Roma; ItaliaFil: Dellarole, Mariano. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Paci, Maurizio. Universita Di Roma; ItaliaFil: de Prat Gay, Gonzalo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaAmerican Chemical Society2006-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/39171Cicero, Daniel Oscar; Nadra, Alejandro Daniel; Eliseo, Tommaso; Dellarole, Mariano; Paci, Maurizio; et al.; Structural and thermodynamic basis for the enhanced transcriptional control by the human papillomavirus strain-16 E2 protein; American Chemical Society; Biochemistry; 45; 21; 5-2006; 6551-65600006-29601520-4995CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://pubs.acs.org/doi/abs/10.1021/bi060123hinfo:eu-repo/semantics/altIdentifier/doi/10.1021/bi060123hinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:11:51Zoai:ri.conicet.gov.ar:11336/39171instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:11:51.555CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Structural and thermodynamic basis for the enhanced transcriptional control by the human papillomavirus strain-16 E2 protein
title Structural and thermodynamic basis for the enhanced transcriptional control by the human papillomavirus strain-16 E2 protein
spellingShingle Structural and thermodynamic basis for the enhanced transcriptional control by the human papillomavirus strain-16 E2 protein
Cicero, Daniel Oscar
Human Papillomavirus
Dna Binding Protein
Nmr
title_short Structural and thermodynamic basis for the enhanced transcriptional control by the human papillomavirus strain-16 E2 protein
title_full Structural and thermodynamic basis for the enhanced transcriptional control by the human papillomavirus strain-16 E2 protein
title_fullStr Structural and thermodynamic basis for the enhanced transcriptional control by the human papillomavirus strain-16 E2 protein
title_full_unstemmed Structural and thermodynamic basis for the enhanced transcriptional control by the human papillomavirus strain-16 E2 protein
title_sort Structural and thermodynamic basis for the enhanced transcriptional control by the human papillomavirus strain-16 E2 protein
dc.creator.none.fl_str_mv Cicero, Daniel Oscar
Nadra, Alejandro Daniel
Eliseo, Tommaso
Dellarole, Mariano
Paci, Maurizio
de Prat Gay, Gonzalo
author Cicero, Daniel Oscar
author_facet Cicero, Daniel Oscar
Nadra, Alejandro Daniel
Eliseo, Tommaso
Dellarole, Mariano
Paci, Maurizio
de Prat Gay, Gonzalo
author_role author
author2 Nadra, Alejandro Daniel
Eliseo, Tommaso
Dellarole, Mariano
Paci, Maurizio
de Prat Gay, Gonzalo
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Human Papillomavirus
Dna Binding Protein
Nmr
topic Human Papillomavirus
Dna Binding Protein
Nmr
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Strain 16 of the human papillomavirus is responsible for the largest number of cases of cervical cancers linked to this virus, and the E2 protein is the transcriptional regulator of all viral genes. We present the first structure for the DNA binding domain of HPV16 E2 bound to DNA, and in particular, to a natural cognate sequence. The NMR structure of the protein backbone reveals that the overall conformation remains virtually unchanged, and chemical shift analysis of the protein bound to a shorter DNA duplex uncovered a contact out of the minimal E2 DNA binding site, made by lysine 349. This contact was confirmed by duration calorimetry and mutagenesis, with a contribution of 1.0 kcal mol-1 to binding energy. HPV16 E2 has the highest DNA binding affinity and exerts a strict transcriptional control, translated into the repression of the E6 and E7 oncogenes. These novel features provide the structural and thermodynamic basis for this tight transcriptional control, the loss of which correlates with carcinogenesis.
Fil: Cicero, Daniel Oscar. Universita Di Roma; Italia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Nadra, Alejandro Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Eliseo, Tommaso. Universita Di Roma; Italia
Fil: Dellarole, Mariano. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Paci, Maurizio. Universita Di Roma; Italia
Fil: de Prat Gay, Gonzalo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
description Strain 16 of the human papillomavirus is responsible for the largest number of cases of cervical cancers linked to this virus, and the E2 protein is the transcriptional regulator of all viral genes. We present the first structure for the DNA binding domain of HPV16 E2 bound to DNA, and in particular, to a natural cognate sequence. The NMR structure of the protein backbone reveals that the overall conformation remains virtually unchanged, and chemical shift analysis of the protein bound to a shorter DNA duplex uncovered a contact out of the minimal E2 DNA binding site, made by lysine 349. This contact was confirmed by duration calorimetry and mutagenesis, with a contribution of 1.0 kcal mol-1 to binding energy. HPV16 E2 has the highest DNA binding affinity and exerts a strict transcriptional control, translated into the repression of the E6 and E7 oncogenes. These novel features provide the structural and thermodynamic basis for this tight transcriptional control, the loss of which correlates with carcinogenesis.
publishDate 2006
dc.date.none.fl_str_mv 2006-05
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/39171
Cicero, Daniel Oscar; Nadra, Alejandro Daniel; Eliseo, Tommaso; Dellarole, Mariano; Paci, Maurizio; et al.; Structural and thermodynamic basis for the enhanced transcriptional control by the human papillomavirus strain-16 E2 protein; American Chemical Society; Biochemistry; 45; 21; 5-2006; 6551-6560
0006-2960
1520-4995
CONICET Digital
CONICET
url http://hdl.handle.net/11336/39171
identifier_str_mv Cicero, Daniel Oscar; Nadra, Alejandro Daniel; Eliseo, Tommaso; Dellarole, Mariano; Paci, Maurizio; et al.; Structural and thermodynamic basis for the enhanced transcriptional control by the human papillomavirus strain-16 E2 protein; American Chemical Society; Biochemistry; 45; 21; 5-2006; 6551-6560
0006-2960
1520-4995
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://pubs.acs.org/doi/abs/10.1021/bi060123h
info:eu-repo/semantics/altIdentifier/doi/10.1021/bi060123h
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Chemical Society
publisher.none.fl_str_mv American Chemical Society
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1842270172963930112
score 13.13397

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