Evolutionary rates in human amyloid proteins reveal their intrinsic metastability

Autores
Zea, Diego Javier; Mac Donagh, Juan; Benítez, Guillermo Ignacio; Guisande Donadio, Cristian Emanuel; Marchetti, Julia; Palopoli, Nicolás; Fornasari, Maria Silvina; Parisi, Gustavo Daniel
Año de publicación
2022
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The emerging picture of protein nature reveals its intrinsic metastability. According to this idea, although a protein is kinetically trapped in a local free energy minimum that defines its native state, those kinetic barriers can be overcome by a complex mixture of the protein’s intrinsic properties and environmental conditions, promoting access to more stable states such as the amyloid fibril. Proteins that are strongly driven towards aggregation in the form of these fibrils are called amyloidogenic. In this work we study the evolutionary rates of 81 human proteins for which an in vivo amyloid state is supported by experiment-based evidence. We found that these proteins evolve faster when compared with a large dataset of ∼16,000 reference proteins from the human proteome. However, their evolutionary rates were indistinguishable from those of secreted proteins that are already known to evolve fast. After analyzing different parameters that correlate with evolutionary rates, we found that the evolutionary rates of amyloidogenic proteins could be modulated by factors associated with metastable transitions such as supersaturation and conformational diversity. Our results showcase the importance of protein metastability in evolutionary studies.
Fil: Zea, Diego Javier. 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. Universite Paris-saclay (universite Paris-saclay);
Fil: Mac Donagh, Juan. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina
Fil: Benítez, Guillermo Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina
Fil: Guisande Donadio, Cristian Emanuel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina
Fil: Marchetti, Julia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina
Fil: Palopoli, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina
Fil: Fornasari, Maria Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina
Fil: Parisi, Gustavo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina
Materia
PROTEIN
EVOLUTION
AMYLOID
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/215809
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/215809
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Evolutionary rates in human amyloid proteins reveal their intrinsic metastabilityZea, Diego JavierMac Donagh, JuanBenítez, Guillermo IgnacioGuisande Donadio, Cristian EmanuelMarchetti, JuliaPalopoli, NicolásFornasari, Maria SilvinaParisi, Gustavo DanielPROTEINEVOLUTIONAMYLOIDhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The emerging picture of protein nature reveals its intrinsic metastability. According to this idea, although a protein is kinetically trapped in a local free energy minimum that defines its native state, those kinetic barriers can be overcome by a complex mixture of the protein’s intrinsic properties and environmental conditions, promoting access to more stable states such as the amyloid fibril. Proteins that are strongly driven towards aggregation in the form of these fibrils are called amyloidogenic. In this work we study the evolutionary rates of 81 human proteins for which an in vivo amyloid state is supported by experiment-based evidence. We found that these proteins evolve faster when compared with a large dataset of ∼16,000 reference proteins from the human proteome. However, their evolutionary rates were indistinguishable from those of secreted proteins that are already known to evolve fast. After analyzing different parameters that correlate with evolutionary rates, we found that the evolutionary rates of amyloidogenic proteins could be modulated by factors associated with metastable transitions such as supersaturation and conformational diversity. Our results showcase the importance of protein metastability in evolutionary studies.Fil: Zea, Diego Javier. 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. Universite Paris-saclay (universite Paris-saclay);Fil: Mac Donagh, Juan. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; ArgentinaFil: Benítez, Guillermo Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; ArgentinaFil: Guisande Donadio, Cristian Emanuel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; ArgentinaFil: Marchetti, Julia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; ArgentinaFil: Palopoli, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; ArgentinaFil: Fornasari, Maria Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; ArgentinaFil: Parisi, Gustavo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; ArgentinaCold Spring Harbor Laboratory Press2022-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/215809Zea, Diego Javier; Mac Donagh, Juan; Benítez, Guillermo Ignacio; Guisande Donadio, Cristian Emanuel; Marchetti, Julia; et al.; Evolutionary rates in human amyloid proteins reveal their intrinsic metastability; Cold Spring Harbor Laboratory Press; bioRxiv; 2022; 9-2022; 1-122692-8205CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.biorxiv.org/content/10.1101/2022.09.07.506994v1info:eu-repo/semantics/altIdentifier/doi/10.1101/2022.09.07.506994info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:56:26Zoai:ri.conicet.gov.ar:11336/215809instacron: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:34982025-10-22 11:56:26.373CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Evolutionary rates in human amyloid proteins reveal their intrinsic metastability
title Evolutionary rates in human amyloid proteins reveal their intrinsic metastability
spellingShingle Evolutionary rates in human amyloid proteins reveal their intrinsic metastability
Zea, Diego Javier
PROTEIN
EVOLUTION
AMYLOID
title_short Evolutionary rates in human amyloid proteins reveal their intrinsic metastability
title_full Evolutionary rates in human amyloid proteins reveal their intrinsic metastability
title_fullStr Evolutionary rates in human amyloid proteins reveal their intrinsic metastability
title_full_unstemmed Evolutionary rates in human amyloid proteins reveal their intrinsic metastability
title_sort Evolutionary rates in human amyloid proteins reveal their intrinsic metastability
dc.creator.none.fl_str_mv Zea, Diego Javier
Mac Donagh, Juan
Benítez, Guillermo Ignacio
Guisande Donadio, Cristian Emanuel
Marchetti, Julia
Palopoli, Nicolás
Fornasari, Maria Silvina
Parisi, Gustavo Daniel
author Zea, Diego Javier
author_facet Zea, Diego Javier
Mac Donagh, Juan
Benítez, Guillermo Ignacio
Guisande Donadio, Cristian Emanuel
Marchetti, Julia
Palopoli, Nicolás
Fornasari, Maria Silvina
Parisi, Gustavo Daniel
author_role author
author2 Mac Donagh, Juan
Benítez, Guillermo Ignacio
Guisande Donadio, Cristian Emanuel
Marchetti, Julia
Palopoli, Nicolás
Fornasari, Maria Silvina
Parisi, Gustavo Daniel
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv PROTEIN
EVOLUTION
AMYLOID
topic PROTEIN
EVOLUTION
AMYLOID
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 emerging picture of protein nature reveals its intrinsic metastability. According to this idea, although a protein is kinetically trapped in a local free energy minimum that defines its native state, those kinetic barriers can be overcome by a complex mixture of the protein’s intrinsic properties and environmental conditions, promoting access to more stable states such as the amyloid fibril. Proteins that are strongly driven towards aggregation in the form of these fibrils are called amyloidogenic. In this work we study the evolutionary rates of 81 human proteins for which an in vivo amyloid state is supported by experiment-based evidence. We found that these proteins evolve faster when compared with a large dataset of ∼16,000 reference proteins from the human proteome. However, their evolutionary rates were indistinguishable from those of secreted proteins that are already known to evolve fast. After analyzing different parameters that correlate with evolutionary rates, we found that the evolutionary rates of amyloidogenic proteins could be modulated by factors associated with metastable transitions such as supersaturation and conformational diversity. Our results showcase the importance of protein metastability in evolutionary studies.
Fil: Zea, Diego Javier. 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. Universite Paris-saclay (universite Paris-saclay);
Fil: Mac Donagh, Juan. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina
Fil: Benítez, Guillermo Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina
Fil: Guisande Donadio, Cristian Emanuel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina
Fil: Marchetti, Julia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina
Fil: Palopoli, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina
Fil: Fornasari, Maria Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina
Fil: Parisi, Gustavo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina
description The emerging picture of protein nature reveals its intrinsic metastability. According to this idea, although a protein is kinetically trapped in a local free energy minimum that defines its native state, those kinetic barriers can be overcome by a complex mixture of the protein’s intrinsic properties and environmental conditions, promoting access to more stable states such as the amyloid fibril. Proteins that are strongly driven towards aggregation in the form of these fibrils are called amyloidogenic. In this work we study the evolutionary rates of 81 human proteins for which an in vivo amyloid state is supported by experiment-based evidence. We found that these proteins evolve faster when compared with a large dataset of ∼16,000 reference proteins from the human proteome. However, their evolutionary rates were indistinguishable from those of secreted proteins that are already known to evolve fast. After analyzing different parameters that correlate with evolutionary rates, we found that the evolutionary rates of amyloidogenic proteins could be modulated by factors associated with metastable transitions such as supersaturation and conformational diversity. Our results showcase the importance of protein metastability in evolutionary studies.
publishDate 2022
dc.date.none.fl_str_mv 2022-09
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/11336/215809
Zea, Diego Javier; Mac Donagh, Juan; Benítez, Guillermo Ignacio; Guisande Donadio, Cristian Emanuel; Marchetti, Julia; et al.; Evolutionary rates in human amyloid proteins reveal their intrinsic metastability; Cold Spring Harbor Laboratory Press; bioRxiv; 2022; 9-2022; 1-12
2692-8205
CONICET Digital
CONICET
url http://hdl.handle.net/11336/215809
identifier_str_mv Zea, Diego Javier; Mac Donagh, Juan; Benítez, Guillermo Ignacio; Guisande Donadio, Cristian Emanuel; Marchetti, Julia; et al.; Evolutionary rates in human amyloid proteins reveal their intrinsic metastability; Cold Spring Harbor Laboratory Press; bioRxiv; 2022; 9-2022; 1-12
2692-8205
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://www.biorxiv.org/content/10.1101/2022.09.07.506994v1
info:eu-repo/semantics/altIdentifier/doi/10.1101/2022.09.07.506994
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Cold Spring Harbor Laboratory Press
publisher.none.fl_str_mv Cold Spring Harbor Laboratory 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 12.982451

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