Deciphering opening mechanisms of 14‐3‐3 proteins

Autores
Barrera Guisasola, Exequiel Ernesto; Skrabana, Rostislav; Bustos, Diego Martin
Año de publicación
2025
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The 14-3-3 proteins are a highly conserved family of regulatory molecules that play crucial roles in various cellular processes. They are known for their ability to bind to phosphorylated serine and threonine residues on target proteins, which allows them to modulate their activity, localization, and stability. In mammals, there are seven known paralogs of 14-3-3 proteins, designated as β, ε, ζ, η, σ, τ, and γ. Each paralog has distinct biological functions and tissue distributions, which allow a diverse range of regulatory roles in cellular processes. The conformational plasticity of 14-3-3s regulates their interaction with protein partners but has not yet been thoroughly characterized. We investigated this topic by classical molecular dynamics simulations and observed how the γ, ε, and ζ paralogs exhibit different opening rates. A PCA analysis identified the main modes of these opening-conformational variations. Using correlation-based tools and simulations with single amino acid substitutions, we have recognized how the amphipathic 14-3-3 groove opening is triggered by a distally located aliphatic-π interaction. The identified residues form a partially conserved small cavity between helices H6, H7, and H8, representing a potential paralog-specific drug site.
Fil: Barrera Guisasola, Exequiel Ernesto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
Fil: Skrabana, Rostislav. Slovak Academy of Sciences. Institute of Botany; Eslovaquia
Fil: Bustos, Diego Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
Materia
14-3-3 PROTEINS
MOLECULAR DYNAMICS
ALLOSTERISMS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/279228
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Deciphering opening mechanisms of 14‐3‐3 proteinsBarrera Guisasola, Exequiel ErnestoSkrabana, RostislavBustos, Diego Martin14-3-3 PROTEINSMOLECULAR DYNAMICSALLOSTERISMShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The 14-3-3 proteins are a highly conserved family of regulatory molecules that play crucial roles in various cellular processes. They are known for their ability to bind to phosphorylated serine and threonine residues on target proteins, which allows them to modulate their activity, localization, and stability. In mammals, there are seven known paralogs of 14-3-3 proteins, designated as β, ε, ζ, η, σ, τ, and γ. Each paralog has distinct biological functions and tissue distributions, which allow a diverse range of regulatory roles in cellular processes. The conformational plasticity of 14-3-3s regulates their interaction with protein partners but has not yet been thoroughly characterized. We investigated this topic by classical molecular dynamics simulations and observed how the γ, ε, and ζ paralogs exhibit different opening rates. A PCA analysis identified the main modes of these opening-conformational variations. Using correlation-based tools and simulations with single amino acid substitutions, we have recognized how the amphipathic 14-3-3 groove opening is triggered by a distally located aliphatic-π interaction. The identified residues form a partially conserved small cavity between helices H6, H7, and H8, representing a potential paralog-specific drug site.Fil: Barrera Guisasola, Exequiel Ernesto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Skrabana, Rostislav. Slovak Academy of Sciences. Institute of Botany; EslovaquiaFil: Bustos, Diego Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaJohn Wiley & Sons2025-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/279228Barrera Guisasola, Exequiel Ernesto; Skrabana, Rostislav; Bustos, Diego Martin; Deciphering opening mechanisms of 14‐3‐3 proteins; John Wiley & Sons; Protein Science; 34; 4; 3-2025; 1-110961-8368CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/10.1002/pro.70108info:eu-repo/semantics/altIdentifier/doi/10.1002/pro.70108info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-02-26T10:12:25Zoai:ri.conicet.gov.ar:11336/279228instacron: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:34982026-02-26 10:12:25.622CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Deciphering opening mechanisms of 14‐3‐3 proteins
title Deciphering opening mechanisms of 14‐3‐3 proteins
spellingShingle Deciphering opening mechanisms of 14‐3‐3 proteins
Barrera Guisasola, Exequiel Ernesto
14-3-3 PROTEINS
MOLECULAR DYNAMICS
ALLOSTERISMS
title_short Deciphering opening mechanisms of 14‐3‐3 proteins
title_full Deciphering opening mechanisms of 14‐3‐3 proteins
title_fullStr Deciphering opening mechanisms of 14‐3‐3 proteins
title_full_unstemmed Deciphering opening mechanisms of 14‐3‐3 proteins
title_sort Deciphering opening mechanisms of 14‐3‐3 proteins
dc.creator.none.fl_str_mv Barrera Guisasola, Exequiel Ernesto
Skrabana, Rostislav
Bustos, Diego Martin
author Barrera Guisasola, Exequiel Ernesto
author_facet Barrera Guisasola, Exequiel Ernesto
Skrabana, Rostislav
Bustos, Diego Martin
author_role author
author2 Skrabana, Rostislav
Bustos, Diego Martin
author2_role author
author
dc.subject.none.fl_str_mv 14-3-3 PROTEINS
MOLECULAR DYNAMICS
ALLOSTERISMS
topic 14-3-3 PROTEINS
MOLECULAR DYNAMICS
ALLOSTERISMS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The 14-3-3 proteins are a highly conserved family of regulatory molecules that play crucial roles in various cellular processes. They are known for their ability to bind to phosphorylated serine and threonine residues on target proteins, which allows them to modulate their activity, localization, and stability. In mammals, there are seven known paralogs of 14-3-3 proteins, designated as β, ε, ζ, η, σ, τ, and γ. Each paralog has distinct biological functions and tissue distributions, which allow a diverse range of regulatory roles in cellular processes. The conformational plasticity of 14-3-3s regulates their interaction with protein partners but has not yet been thoroughly characterized. We investigated this topic by classical molecular dynamics simulations and observed how the γ, ε, and ζ paralogs exhibit different opening rates. A PCA analysis identified the main modes of these opening-conformational variations. Using correlation-based tools and simulations with single amino acid substitutions, we have recognized how the amphipathic 14-3-3 groove opening is triggered by a distally located aliphatic-π interaction. The identified residues form a partially conserved small cavity between helices H6, H7, and H8, representing a potential paralog-specific drug site.
Fil: Barrera Guisasola, Exequiel Ernesto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
Fil: Skrabana, Rostislav. Slovak Academy of Sciences. Institute of Botany; Eslovaquia
Fil: Bustos, Diego Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
description The 14-3-3 proteins are a highly conserved family of regulatory molecules that play crucial roles in various cellular processes. They are known for their ability to bind to phosphorylated serine and threonine residues on target proteins, which allows them to modulate their activity, localization, and stability. In mammals, there are seven known paralogs of 14-3-3 proteins, designated as β, ε, ζ, η, σ, τ, and γ. Each paralog has distinct biological functions and tissue distributions, which allow a diverse range of regulatory roles in cellular processes. The conformational plasticity of 14-3-3s regulates their interaction with protein partners but has not yet been thoroughly characterized. We investigated this topic by classical molecular dynamics simulations and observed how the γ, ε, and ζ paralogs exhibit different opening rates. A PCA analysis identified the main modes of these opening-conformational variations. Using correlation-based tools and simulations with single amino acid substitutions, we have recognized how the amphipathic 14-3-3 groove opening is triggered by a distally located aliphatic-π interaction. The identified residues form a partially conserved small cavity between helices H6, H7, and H8, representing a potential paralog-specific drug site.
publishDate 2025
dc.date.none.fl_str_mv 2025-03
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/11336/279228
Barrera Guisasola, Exequiel Ernesto; Skrabana, Rostislav; Bustos, Diego Martin; Deciphering opening mechanisms of 14‐3‐3 proteins; John Wiley & Sons; Protein Science; 34; 4; 3-2025; 1-11
0961-8368
CONICET Digital
CONICET
url http://hdl.handle.net/11336/279228
identifier_str_mv Barrera Guisasola, Exequiel Ernesto; Skrabana, Rostislav; Bustos, Diego Martin; Deciphering opening mechanisms of 14‐3‐3 proteins; John Wiley & Sons; Protein Science; 34; 4; 3-2025; 1-11
0961-8368
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://onlinelibrary.wiley.com/doi/10.1002/pro.70108
info:eu-repo/semantics/altIdentifier/doi/10.1002/pro.70108
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv John Wiley & Sons
publisher.none.fl_str_mv John Wiley & Sons
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 13.176822

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