Copper(II) and the pathological H50Q α-synuclein mutant: Environment meets genetics

Autores
Villar Piqué, Anna; Rossetti, Giulia; Ventura, Salvador; Carloni, Paolo; Fernandez, Claudio Oscar; Outeiro, Tiago Fleming
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Copper is one of the metals described to bind the Parkinson disease-related protein α-synuclein (aSyn), and to promote its aggregation. Although histidine at position 50 in the aSyn sequence is one of the most studied copper-anchoring sites, its precise role in copper binding and aSyn aggregation is still unclear. Previous studies suggested that this residue does not significantly affect copper-mediated aSyn aggregation. However, our findings showed that the aggregation of the pathological H50Q aSyn mutant is enhanced by copper hints otherwise. Despite the inexistence of a model for aSyn H50Q-copper complexation, we discuss possible mechanisms by which this metal contributes to the misfolding and self-assembly of this particular aSyn mutant. Considering the genetic association of the H50Q mutation with familial forms of Parkinson disease, and the fact that copper homeostasis is deregulated in this disorder, understanding the interplay between both factors will shed light into the molecular and cellular mechanisms triggering the development and spreading of the aSyn pathology.
Fil: Villar Piqué, Anna. University Medical Centre Gottingen; Alemania
Fil: Rossetti, Giulia. Institute for Advanced Simulation; Alemania. Westfalische Technische Hochschule Aachen University; Alemania. Julich Supercomputing Centre; Alemania
Fil: Ventura, Salvador. Universitat Autònoma de Barcelona; España
Fil: Carloni, Paolo. Institute for Advanced Simulation; Alemania
Fil: Fernandez, Claudio Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina. Max Planck Laboratory for Structural Biology; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Investigaciones Para El Descubrimiento de Farmacos de Rosario. Universidad Nacional de Rosario. Instituto de Investigaciones Para El Descubrimiento de Farmacos de Rosario; Argentina
Fil: Outeiro, Tiago Fleming. University Medical Centre Gottingen; Alemania. Max Planck Institute for Experimental Medicine; Alemania
Materia
AMYLOID
COPPER
H50Q MUTATION
PARKINSON DISEASE
PROTEIN AGGREGATION
Α-SYNUCLEIN
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:11336/50317
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/50317
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Copper(II) and the pathological H50Q α-synuclein mutant: Environment meets geneticsVillar Piqué, AnnaRossetti, GiuliaVentura, SalvadorCarloni, PaoloFernandez, Claudio OscarOuteiro, Tiago FlemingAMYLOIDCOPPERH50Q MUTATIONPARKINSON DISEASEPROTEIN AGGREGATIONΑ-SYNUCLEINhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Copper is one of the metals described to bind the Parkinson disease-related protein α-synuclein (aSyn), and to promote its aggregation. Although histidine at position 50 in the aSyn sequence is one of the most studied copper-anchoring sites, its precise role in copper binding and aSyn aggregation is still unclear. Previous studies suggested that this residue does not significantly affect copper-mediated aSyn aggregation. However, our findings showed that the aggregation of the pathological H50Q aSyn mutant is enhanced by copper hints otherwise. Despite the inexistence of a model for aSyn H50Q-copper complexation, we discuss possible mechanisms by which this metal contributes to the misfolding and self-assembly of this particular aSyn mutant. Considering the genetic association of the H50Q mutation with familial forms of Parkinson disease, and the fact that copper homeostasis is deregulated in this disorder, understanding the interplay between both factors will shed light into the molecular and cellular mechanisms triggering the development and spreading of the aSyn pathology.Fil: Villar Piqué, Anna. University Medical Centre Gottingen; AlemaniaFil: Rossetti, Giulia. Institute for Advanced Simulation; Alemania. Westfalische Technische Hochschule Aachen University; Alemania. Julich Supercomputing Centre; AlemaniaFil: Ventura, Salvador. Universitat Autònoma de Barcelona; EspañaFil: Carloni, Paolo. Institute for Advanced Simulation; AlemaniaFil: Fernandez, Claudio Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina. Max Planck Laboratory for Structural Biology; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Investigaciones Para El Descubrimiento de Farmacos de Rosario. Universidad Nacional de Rosario. Instituto de Investigaciones Para El Descubrimiento de Farmacos de Rosario; ArgentinaFil: Outeiro, Tiago Fleming. University Medical Centre Gottingen; Alemania. Max Planck Institute for Experimental Medicine; AlemaniaTaylor and Francis Inc.2017-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/50317Villar Piqué, Anna; Rossetti, Giulia; Ventura, Salvador; Carloni, Paolo; Fernandez, Claudio Oscar; et al.; Copper(II) and the pathological H50Q α-synuclein mutant: Environment meets genetics; Taylor and Francis Inc.; Communicative and Integrative Biology; 10; 1; 1-2017; 1-41942-0889CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1080/19420889.2016.1270484info:eu-repo/semantics/altIdentifier/url/https://www.tandfonline.com/doi/full/10.1080/19420889.2016.1270484info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:58:34Zoai:ri.conicet.gov.ar:11336/50317instacron: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 09:58:34.571CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Copper(II) and the pathological H50Q α-synuclein mutant: Environment meets genetics
title Copper(II) and the pathological H50Q α-synuclein mutant: Environment meets genetics
spellingShingle Copper(II) and the pathological H50Q α-synuclein mutant: Environment meets genetics
Villar Piqué, Anna
AMYLOID
COPPER
H50Q MUTATION
PARKINSON DISEASE
PROTEIN AGGREGATION
Α-SYNUCLEIN
title_short Copper(II) and the pathological H50Q α-synuclein mutant: Environment meets genetics
title_full Copper(II) and the pathological H50Q α-synuclein mutant: Environment meets genetics
title_fullStr Copper(II) and the pathological H50Q α-synuclein mutant: Environment meets genetics
title_full_unstemmed Copper(II) and the pathological H50Q α-synuclein mutant: Environment meets genetics
title_sort Copper(II) and the pathological H50Q α-synuclein mutant: Environment meets genetics
dc.creator.none.fl_str_mv Villar Piqué, Anna
Rossetti, Giulia
Ventura, Salvador
Carloni, Paolo
Fernandez, Claudio Oscar
Outeiro, Tiago Fleming
author Villar Piqué, Anna
author_facet Villar Piqué, Anna
Rossetti, Giulia
Ventura, Salvador
Carloni, Paolo
Fernandez, Claudio Oscar
Outeiro, Tiago Fleming
author_role author
author2 Rossetti, Giulia
Ventura, Salvador
Carloni, Paolo
Fernandez, Claudio Oscar
Outeiro, Tiago Fleming
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv AMYLOID
COPPER
H50Q MUTATION
PARKINSON DISEASE
PROTEIN AGGREGATION
Α-SYNUCLEIN
topic AMYLOID
COPPER
H50Q MUTATION
PARKINSON DISEASE
PROTEIN AGGREGATION
Α-SYNUCLEIN
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Copper is one of the metals described to bind the Parkinson disease-related protein α-synuclein (aSyn), and to promote its aggregation. Although histidine at position 50 in the aSyn sequence is one of the most studied copper-anchoring sites, its precise role in copper binding and aSyn aggregation is still unclear. Previous studies suggested that this residue does not significantly affect copper-mediated aSyn aggregation. However, our findings showed that the aggregation of the pathological H50Q aSyn mutant is enhanced by copper hints otherwise. Despite the inexistence of a model for aSyn H50Q-copper complexation, we discuss possible mechanisms by which this metal contributes to the misfolding and self-assembly of this particular aSyn mutant. Considering the genetic association of the H50Q mutation with familial forms of Parkinson disease, and the fact that copper homeostasis is deregulated in this disorder, understanding the interplay between both factors will shed light into the molecular and cellular mechanisms triggering the development and spreading of the aSyn pathology.
Fil: Villar Piqué, Anna. University Medical Centre Gottingen; Alemania
Fil: Rossetti, Giulia. Institute for Advanced Simulation; Alemania. Westfalische Technische Hochschule Aachen University; Alemania. Julich Supercomputing Centre; Alemania
Fil: Ventura, Salvador. Universitat Autònoma de Barcelona; España
Fil: Carloni, Paolo. Institute for Advanced Simulation; Alemania
Fil: Fernandez, Claudio Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina. Max Planck Laboratory for Structural Biology; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Investigaciones Para El Descubrimiento de Farmacos de Rosario. Universidad Nacional de Rosario. Instituto de Investigaciones Para El Descubrimiento de Farmacos de Rosario; Argentina
Fil: Outeiro, Tiago Fleming. University Medical Centre Gottingen; Alemania. Max Planck Institute for Experimental Medicine; Alemania
description Copper is one of the metals described to bind the Parkinson disease-related protein α-synuclein (aSyn), and to promote its aggregation. Although histidine at position 50 in the aSyn sequence is one of the most studied copper-anchoring sites, its precise role in copper binding and aSyn aggregation is still unclear. Previous studies suggested that this residue does not significantly affect copper-mediated aSyn aggregation. However, our findings showed that the aggregation of the pathological H50Q aSyn mutant is enhanced by copper hints otherwise. Despite the inexistence of a model for aSyn H50Q-copper complexation, we discuss possible mechanisms by which this metal contributes to the misfolding and self-assembly of this particular aSyn mutant. Considering the genetic association of the H50Q mutation with familial forms of Parkinson disease, and the fact that copper homeostasis is deregulated in this disorder, understanding the interplay between both factors will shed light into the molecular and cellular mechanisms triggering the development and spreading of the aSyn pathology.
publishDate 2017
dc.date.none.fl_str_mv 2017-01
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/11336/50317
Villar Piqué, Anna; Rossetti, Giulia; Ventura, Salvador; Carloni, Paolo; Fernandez, Claudio Oscar; et al.; Copper(II) and the pathological H50Q α-synuclein mutant: Environment meets genetics; Taylor and Francis Inc.; Communicative and Integrative Biology; 10; 1; 1-2017; 1-4
1942-0889
CONICET Digital
CONICET
url http://hdl.handle.net/11336/50317
identifier_str_mv Villar Piqué, Anna; Rossetti, Giulia; Ventura, Salvador; Carloni, Paolo; Fernandez, Claudio Oscar; et al.; Copper(II) and the pathological H50Q α-synuclein mutant: Environment meets genetics; Taylor and Francis Inc.; Communicative and Integrative Biology; 10; 1; 1-2017; 1-4
1942-0889
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1080/19420889.2016.1270484
info:eu-repo/semantics/altIdentifier/url/https://www.tandfonline.com/doi/full/10.1080/19420889.2016.1270484
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 Taylor and Francis Inc.
publisher.none.fl_str_mv Taylor and Francis Inc.
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_ 1842269528633901056
score 13.13397

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