Conformational dissection of a viral intrinsically disordered domain involved in cellular transformation

Autores
Noval, María Gabriela; Gallo, Mariana; Perrone, Sebastián; Salvay, Andrés Gerardo; Chemes, Lucia Beatriz; de Prat Gay, Gonzalo
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Intrinsic disorder is abundant in viral genomes and provides conformational plasticity to its protein products. In order to gain insight into its structure-function relationships, we carried out a comprehensive analysis of structural propensities within the intrinsically disordered N-terminal domain from the human papillomavirus type-16 E7 oncoprotein (E7N). Two E7N segments located within the conserved CR1 and CR2 regions present transient α-helix structure. The helix in the CR1 region spans residues L8 to L13 and overlaps with the E2F mimic linear motif. The second helix, located within the highly acidic CR2 region, presents a pH-dependent structural transition. At neutral pH the helix spans residues P17 to N29, which include the retinoblastoma tumor suppressor LxCxE binding motif (residues 21?29), while the acidic CKII-PEST region spanning residues E33 to I38 populates polyproline type II (PII) structure. At pH 5.0, the CR2 helix propagates up to residue I38 at the expense of loss of PII due to charge neutralization of acidic residues. Using truncated forms of HPV-16 E7, we confirmed that pH-induced changes in α-helix content are governed by the intrinsically disordered E7N domain. Interestingly, while at both pH the region encompassing the LxCxE motif adopts α-helical structure, the isolated 21?29 fragment including this stretch is unable to populate an α-helix even at high TFE concentrations. Thus, the E7N domain can populate dynamic but discrete structural ensembles by sampling α-helix-coil-PII-ß-sheet structures. This high plasticity may modulate the exposure of linear binding motifs responsible for its multi-target binding properties, leading to interference with key cell signaling pathways and eventually to cellular transformation by the virus.
Fil: Noval, María Gabriela. Fundación Instituto Leloir. Laboratorio de Estructura-Fusión e Ingeniería de Proteínas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires(i); Argentina
Fil: Gallo, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires(i); Argentina. Fundación Instituto Leloir. Laboratorio de Resonancia Magnética Nuclear; Argentina
Fil: Perrone, Sebastián. Fundación Instituto Leloir. Laboratorio de Estructura-Fusión e Ingeniería de Proteínas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina
Fil: Salvay, Andrés Gerardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - La Plata. Instituto de Física de Líquidos y Sistemas Biológicos (i); Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnologia; Argentina
Fil: Chemes, Lucia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires(i); Argentina. Fundación Instituto Leloir. Laboratorio de Estructura-Fusión e Ingeniería de Proteínas; Argentina
Fil: de Prat Gay, Gonzalo. Fundación Instituto Leloir. Laboratorio de Estructura-Fusión e Ingeniería de Proteínas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires(i); Argentina
Materia
INTRINSICALLY DISORDERED PROTEINS
CONFORMATIONAL TRANSITIONS
VIRAL PROTEINS
NMR
IDP
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:11336/1670
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/1670
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Conformational dissection of a viral intrinsically disordered domain involved in cellular transformationNoval, María GabrielaGallo, MarianaPerrone, SebastiánSalvay, Andrés GerardoChemes, Lucia Beatrizde Prat Gay, GonzaloINTRINSICALLY DISORDERED PROTEINSCONFORMATIONAL TRANSITIONSVIRAL PROTEINSNMRIDPhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Intrinsic disorder is abundant in viral genomes and provides conformational plasticity to its protein products. In order to gain insight into its structure-function relationships, we carried out a comprehensive analysis of structural propensities within the intrinsically disordered N-terminal domain from the human papillomavirus type-16 E7 oncoprotein (E7N). Two E7N segments located within the conserved CR1 and CR2 regions present transient α-helix structure. The helix in the CR1 region spans residues L8 to L13 and overlaps with the E2F mimic linear motif. The second helix, located within the highly acidic CR2 region, presents a pH-dependent structural transition. At neutral pH the helix spans residues P17 to N29, which include the retinoblastoma tumor suppressor LxCxE binding motif (residues 21?29), while the acidic CKII-PEST region spanning residues E33 to I38 populates polyproline type II (PII) structure. At pH 5.0, the CR2 helix propagates up to residue I38 at the expense of loss of PII due to charge neutralization of acidic residues. Using truncated forms of HPV-16 E7, we confirmed that pH-induced changes in α-helix content are governed by the intrinsically disordered E7N domain. Interestingly, while at both pH the region encompassing the LxCxE motif adopts α-helical structure, the isolated 21?29 fragment including this stretch is unable to populate an α-helix even at high TFE concentrations. Thus, the E7N domain can populate dynamic but discrete structural ensembles by sampling α-helix-coil-PII-ß-sheet structures. This high plasticity may modulate the exposure of linear binding motifs responsible for its multi-target binding properties, leading to interference with key cell signaling pathways and eventually to cellular transformation by the virus.Fil: Noval, María Gabriela. Fundación Instituto Leloir. Laboratorio de Estructura-Fusión e Ingeniería de Proteínas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires(i); ArgentinaFil: Gallo, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires(i); Argentina. Fundación Instituto Leloir. Laboratorio de Resonancia Magnética Nuclear; ArgentinaFil: Perrone, Sebastián. Fundación Instituto Leloir. Laboratorio de Estructura-Fusión e Ingeniería de Proteínas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; ArgentinaFil: Salvay, Andrés Gerardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - La Plata. Instituto de Física de Líquidos y Sistemas Biológicos (i); Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnologia; ArgentinaFil: Chemes, Lucia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires(i); Argentina. Fundación Instituto Leloir. Laboratorio de Estructura-Fusión e Ingeniería de Proteínas; ArgentinaFil: de Prat Gay, Gonzalo. Fundación Instituto Leloir. Laboratorio de Estructura-Fusión e Ingeniería de Proteínas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires(i); ArgentinaPublic Library of Science2013-09-27info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/1670Noval, María Gabriela; Gallo, Mariana; Perrone, Sebastián; Salvay, Andrés Gerardo; Chemes, Lucia Beatriz; et al.; Conformational dissection of a viral intrinsically disordered domain involved in cellular transformation; Public Library of Science; Plos One; 8; 9; 27-9-2013; 1-171932-6203enginfo:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0072760info:eu-repo/semantics/altIdentifier/url/http://www.iflysib.unlp.edu.ar/sites/default/files/journal.pone_.0072760.pdfinfo:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0072760info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:05:44Zoai:ri.conicet.gov.ar:11336/1670instacron: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 10:05:44.566CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Conformational dissection of a viral intrinsically disordered domain involved in cellular transformation
title Conformational dissection of a viral intrinsically disordered domain involved in cellular transformation
spellingShingle Conformational dissection of a viral intrinsically disordered domain involved in cellular transformation
Noval, María Gabriela
INTRINSICALLY DISORDERED PROTEINS
CONFORMATIONAL TRANSITIONS
VIRAL PROTEINS
NMR
IDP
title_short Conformational dissection of a viral intrinsically disordered domain involved in cellular transformation
title_full Conformational dissection of a viral intrinsically disordered domain involved in cellular transformation
title_fullStr Conformational dissection of a viral intrinsically disordered domain involved in cellular transformation
title_full_unstemmed Conformational dissection of a viral intrinsically disordered domain involved in cellular transformation
title_sort Conformational dissection of a viral intrinsically disordered domain involved in cellular transformation
dc.creator.none.fl_str_mv Noval, María Gabriela
Gallo, Mariana
Perrone, Sebastián
Salvay, Andrés Gerardo
Chemes, Lucia Beatriz
de Prat Gay, Gonzalo
author Noval, María Gabriela
author_facet Noval, María Gabriela
Gallo, Mariana
Perrone, Sebastián
Salvay, Andrés Gerardo
Chemes, Lucia Beatriz
de Prat Gay, Gonzalo
author_role author
author2 Gallo, Mariana
Perrone, Sebastián
Salvay, Andrés Gerardo
Chemes, Lucia Beatriz
de Prat Gay, Gonzalo
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv INTRINSICALLY DISORDERED PROTEINS
CONFORMATIONAL TRANSITIONS
VIRAL PROTEINS
NMR
IDP
topic INTRINSICALLY DISORDERED PROTEINS
CONFORMATIONAL TRANSITIONS
VIRAL PROTEINS
NMR
IDP
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Intrinsic disorder is abundant in viral genomes and provides conformational plasticity to its protein products. In order to gain insight into its structure-function relationships, we carried out a comprehensive analysis of structural propensities within the intrinsically disordered N-terminal domain from the human papillomavirus type-16 E7 oncoprotein (E7N). Two E7N segments located within the conserved CR1 and CR2 regions present transient α-helix structure. The helix in the CR1 region spans residues L8 to L13 and overlaps with the E2F mimic linear motif. The second helix, located within the highly acidic CR2 region, presents a pH-dependent structural transition. At neutral pH the helix spans residues P17 to N29, which include the retinoblastoma tumor suppressor LxCxE binding motif (residues 21?29), while the acidic CKII-PEST region spanning residues E33 to I38 populates polyproline type II (PII) structure. At pH 5.0, the CR2 helix propagates up to residue I38 at the expense of loss of PII due to charge neutralization of acidic residues. Using truncated forms of HPV-16 E7, we confirmed that pH-induced changes in α-helix content are governed by the intrinsically disordered E7N domain. Interestingly, while at both pH the region encompassing the LxCxE motif adopts α-helical structure, the isolated 21?29 fragment including this stretch is unable to populate an α-helix even at high TFE concentrations. Thus, the E7N domain can populate dynamic but discrete structural ensembles by sampling α-helix-coil-PII-ß-sheet structures. This high plasticity may modulate the exposure of linear binding motifs responsible for its multi-target binding properties, leading to interference with key cell signaling pathways and eventually to cellular transformation by the virus.
Fil: Noval, María Gabriela. Fundación Instituto Leloir. Laboratorio de Estructura-Fusión e Ingeniería de Proteínas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires(i); Argentina
Fil: Gallo, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires(i); Argentina. Fundación Instituto Leloir. Laboratorio de Resonancia Magnética Nuclear; Argentina
Fil: Perrone, Sebastián. Fundación Instituto Leloir. Laboratorio de Estructura-Fusión e Ingeniería de Proteínas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina
Fil: Salvay, Andrés Gerardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - La Plata. Instituto de Física de Líquidos y Sistemas Biológicos (i); Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnologia; Argentina
Fil: Chemes, Lucia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires(i); Argentina. Fundación Instituto Leloir. Laboratorio de Estructura-Fusión e Ingeniería de Proteínas; Argentina
Fil: de Prat Gay, Gonzalo. Fundación Instituto Leloir. Laboratorio de Estructura-Fusión e Ingeniería de Proteínas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires(i); Argentina
description Intrinsic disorder is abundant in viral genomes and provides conformational plasticity to its protein products. In order to gain insight into its structure-function relationships, we carried out a comprehensive analysis of structural propensities within the intrinsically disordered N-terminal domain from the human papillomavirus type-16 E7 oncoprotein (E7N). Two E7N segments located within the conserved CR1 and CR2 regions present transient α-helix structure. The helix in the CR1 region spans residues L8 to L13 and overlaps with the E2F mimic linear motif. The second helix, located within the highly acidic CR2 region, presents a pH-dependent structural transition. At neutral pH the helix spans residues P17 to N29, which include the retinoblastoma tumor suppressor LxCxE binding motif (residues 21?29), while the acidic CKII-PEST region spanning residues E33 to I38 populates polyproline type II (PII) structure. At pH 5.0, the CR2 helix propagates up to residue I38 at the expense of loss of PII due to charge neutralization of acidic residues. Using truncated forms of HPV-16 E7, we confirmed that pH-induced changes in α-helix content are governed by the intrinsically disordered E7N domain. Interestingly, while at both pH the region encompassing the LxCxE motif adopts α-helical structure, the isolated 21?29 fragment including this stretch is unable to populate an α-helix even at high TFE concentrations. Thus, the E7N domain can populate dynamic but discrete structural ensembles by sampling α-helix-coil-PII-ß-sheet structures. This high plasticity may modulate the exposure of linear binding motifs responsible for its multi-target binding properties, leading to interference with key cell signaling pathways and eventually to cellular transformation by the virus.
publishDate 2013
dc.date.none.fl_str_mv 2013-09-27
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/11336/1670
Noval, María Gabriela; Gallo, Mariana; Perrone, Sebastián; Salvay, Andrés Gerardo; Chemes, Lucia Beatriz; et al.; Conformational dissection of a viral intrinsically disordered domain involved in cellular transformation; Public Library of Science; Plos One; 8; 9; 27-9-2013; 1-17
1932-6203
url http://hdl.handle.net/11336/1670
identifier_str_mv Noval, María Gabriela; Gallo, Mariana; Perrone, Sebastián; Salvay, Andrés Gerardo; Chemes, Lucia Beatriz; et al.; Conformational dissection of a viral intrinsically disordered domain involved in cellular transformation; Public Library of Science; Plos One; 8; 9; 27-9-2013; 1-17
1932-6203
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0072760
info:eu-repo/semantics/altIdentifier/url/http://www.iflysib.unlp.edu.ar/sites/default/files/journal.pone_.0072760.pdf
info:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0072760
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
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
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
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