Mutational analysis of kinetic partitioning in protein folding and protein-DNA binding

Autores
Sánchez Miguel, Ignacio Enrique; Ferreiro, Diego; de Prat Gay, Gonzalo
Año de publicación
2011
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Kinetic partitioning between competing routes is present in many biological processes. Here, we propose a methodology to characterize kinetic partitioning through site-directed mutagenesis and apply it to parallel routes for unfolding of the TI I27 protein and for recognition of its target DNA by the human papillomavirus E2 protein. The balance between the two competing reaction routes can be quantified by the partitioning constant K(p). K(p) is easily modulated by point mutations, opening the way for the rational design of kinetic partitioning. Conserved wild-type residues strongly favor one of the two competing reactions, suggesting that in these systems there is an evolutionary pressure to shift partitioning towards a certain route. The mutations with the largest effects on partitioning cluster together in space, defining the protein regions most relevant for the modulation of partitioning. Such regions are neither fully coincident with nor strictly segregated from the regions that are important from each competing reaction. We dissected the mutational effects on partitioning into the contributions from each competing route using a new parameter called pi-value. The results suggest how the design of kinetic partitioning may be approached in each case.
Fil: Sánchez Miguel, Ignacio Enrique. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Ferreiro, Diego. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina
Fil: de Prat Gay, Gonzalo. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina
Materia
Kinetic Partitioning
Point Mutation
Protein Design
Protein-Dna Binding
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:11336/15240
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/15240
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Mutational analysis of kinetic partitioning in protein folding and protein-DNA bindingSánchez Miguel, Ignacio EnriqueFerreiro, Diegode Prat Gay, GonzaloKinetic PartitioningPoint MutationProtein DesignProtein-Dna Bindinghttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Kinetic partitioning between competing routes is present in many biological processes. Here, we propose a methodology to characterize kinetic partitioning through site-directed mutagenesis and apply it to parallel routes for unfolding of the TI I27 protein and for recognition of its target DNA by the human papillomavirus E2 protein. The balance between the two competing reaction routes can be quantified by the partitioning constant K(p). K(p) is easily modulated by point mutations, opening the way for the rational design of kinetic partitioning. Conserved wild-type residues strongly favor one of the two competing reactions, suggesting that in these systems there is an evolutionary pressure to shift partitioning towards a certain route. The mutations with the largest effects on partitioning cluster together in space, defining the protein regions most relevant for the modulation of partitioning. Such regions are neither fully coincident with nor strictly segregated from the regions that are important from each competing reaction. We dissected the mutational effects on partitioning into the contributions from each competing route using a new parameter called pi-value. The results suggest how the design of kinetic partitioning may be approached in each case.Fil: Sánchez Miguel, Ignacio Enrique. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Ferreiro, Diego. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: de Prat Gay, Gonzalo. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; ArgentinaOxford University Press2011-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/15240Sánchez Miguel, Ignacio Enrique; Ferreiro, Diego; de Prat Gay, Gonzalo; Mutational analysis of kinetic partitioning in protein folding and protein-DNA binding; Oxford University Press; Protein Engineering Design & Selection; 24; 1-2; 1-2011; 179-1841741-0126enginfo:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/peds/article-lookup/doi/10.1093/protein/gzq064info:eu-repo/semantics/altIdentifier/doi/10.1093/protein/gzq064info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3003449/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:09:12Zoai:ri.conicet.gov.ar:11336/15240instacron: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:34982025-09-10 13:09:13.073CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Mutational analysis of kinetic partitioning in protein folding and protein-DNA binding
title Mutational analysis of kinetic partitioning in protein folding and protein-DNA binding
spellingShingle Mutational analysis of kinetic partitioning in protein folding and protein-DNA binding
Sánchez Miguel, Ignacio Enrique
Kinetic Partitioning
Point Mutation
Protein Design
Protein-Dna Binding
title_short Mutational analysis of kinetic partitioning in protein folding and protein-DNA binding
title_full Mutational analysis of kinetic partitioning in protein folding and protein-DNA binding
title_fullStr Mutational analysis of kinetic partitioning in protein folding and protein-DNA binding
title_full_unstemmed Mutational analysis of kinetic partitioning in protein folding and protein-DNA binding
title_sort Mutational analysis of kinetic partitioning in protein folding and protein-DNA binding
dc.creator.none.fl_str_mv Sánchez Miguel, Ignacio Enrique
Ferreiro, Diego
de Prat Gay, Gonzalo
author Sánchez Miguel, Ignacio Enrique
author_facet Sánchez Miguel, Ignacio Enrique
Ferreiro, Diego
de Prat Gay, Gonzalo
author_role author
author2 Ferreiro, Diego
de Prat Gay, Gonzalo
author2_role author
author
dc.subject.none.fl_str_mv Kinetic Partitioning
Point Mutation
Protein Design
Protein-Dna Binding
topic Kinetic Partitioning
Point Mutation
Protein Design
Protein-Dna Binding
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Kinetic partitioning between competing routes is present in many biological processes. Here, we propose a methodology to characterize kinetic partitioning through site-directed mutagenesis and apply it to parallel routes for unfolding of the TI I27 protein and for recognition of its target DNA by the human papillomavirus E2 protein. The balance between the two competing reaction routes can be quantified by the partitioning constant K(p). K(p) is easily modulated by point mutations, opening the way for the rational design of kinetic partitioning. Conserved wild-type residues strongly favor one of the two competing reactions, suggesting that in these systems there is an evolutionary pressure to shift partitioning towards a certain route. The mutations with the largest effects on partitioning cluster together in space, defining the protein regions most relevant for the modulation of partitioning. Such regions are neither fully coincident with nor strictly segregated from the regions that are important from each competing reaction. We dissected the mutational effects on partitioning into the contributions from each competing route using a new parameter called pi-value. The results suggest how the design of kinetic partitioning may be approached in each case.
Fil: Sánchez Miguel, Ignacio Enrique. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Ferreiro, Diego. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina
Fil: de Prat Gay, Gonzalo. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina
description Kinetic partitioning between competing routes is present in many biological processes. Here, we propose a methodology to characterize kinetic partitioning through site-directed mutagenesis and apply it to parallel routes for unfolding of the TI I27 protein and for recognition of its target DNA by the human papillomavirus E2 protein. The balance between the two competing reaction routes can be quantified by the partitioning constant K(p). K(p) is easily modulated by point mutations, opening the way for the rational design of kinetic partitioning. Conserved wild-type residues strongly favor one of the two competing reactions, suggesting that in these systems there is an evolutionary pressure to shift partitioning towards a certain route. The mutations with the largest effects on partitioning cluster together in space, defining the protein regions most relevant for the modulation of partitioning. Such regions are neither fully coincident with nor strictly segregated from the regions that are important from each competing reaction. We dissected the mutational effects on partitioning into the contributions from each competing route using a new parameter called pi-value. The results suggest how the design of kinetic partitioning may be approached in each case.
publishDate 2011
dc.date.none.fl_str_mv 2011-01
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/11336/15240
Sánchez Miguel, Ignacio Enrique; Ferreiro, Diego; de Prat Gay, Gonzalo; Mutational analysis of kinetic partitioning in protein folding and protein-DNA binding; Oxford University Press; Protein Engineering Design & Selection; 24; 1-2; 1-2011; 179-184
1741-0126
url http://hdl.handle.net/11336/15240
identifier_str_mv Sánchez Miguel, Ignacio Enrique; Ferreiro, Diego; de Prat Gay, Gonzalo; Mutational analysis of kinetic partitioning in protein folding and protein-DNA binding; Oxford University Press; Protein Engineering Design & Selection; 24; 1-2; 1-2011; 179-184
1741-0126
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/peds/article-lookup/doi/10.1093/protein/gzq064
info:eu-repo/semantics/altIdentifier/doi/10.1093/protein/gzq064
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3003449/
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
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
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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score 12.993085

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