Structural remodeling during amyloidogenesis of physiological Nα-acetylated α-synuclein

Autores
Gallea, Jose Ignacio; Sarroukh, Rabia; Yunes Quartino, Pablo Javier; Ruysschaert, Jean-Marie; Raussens, Vincent; Celej, Maria Soledad
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The misfolding and aggregation of the presynaptic protein α-synuclein (AS) into amyloid fibrils is pathognomonic of Parkinson's disease, though the mechanism by which this structural conversion occurs is largely unknown. Soluble oligomeric species that accumulate as intermediates in the process of fibril formation are thought to be highly cytotoxic. Recent studies indicate that oligomer-to-fibril AS transition plays a key role in cell toxicity and progression of neurodegeneration. We previously demonstrated that a subgroup of oligomeric AS species are ordered assemblies possessing a well-defined pattern of intermolecular contacts which are arranged into a distinctive antiparallel β-sheet structure, as opposed to the parallel fibrillar fold. Recently, it was demonstrated that the physiological form of AS is N-terminally acetylated (Ac-AS). Here, we first showed that well-characterized conformational ensembles of Ac-AS, namely monomers, oligomers and fibrils, recapitulate many biophysical features of the nonacetylated protein, such as hydrodynamic, tinctorial, structural and membrane-leakage properties. Then, we relied on ATR-FTIR spectroscopy to explore the structural reorganization during Ac-AS fibrillogenesis. We found that antiparallel β-sheet transient intermediates are built-up at early stages of aggregation, which then evolve to parallel β-sheet fibrils through helix-rich/disordered species. The results are discussed in terms of regions of the protein that might participate in this structural rearrangement. Our work provides new insights into the complex conformational reorganization occurring during Ac-AS amyloid formation.
Fil: Gallea, Jose Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina
Fil: Sarroukh, Rabia. Université Libre de Bruxelles; Bélgica
Fil: Yunes Quartino, Pablo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Ciencia y Tecnología de Alimentos Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Ciencia y Tecnología de Alimentos Córdoba; Argentina
Fil: Ruysschaert, Jean-Marie. Université Libre de Bruxelles; Bélgica
Fil: Raussens, Vincent. Université Libre de Bruxelles; Bélgica
Fil: Celej, Maria Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina
Materia
Acetylated-Synuclein
Amyloid
Fibrillation
Ftir
Parkinson'S Disease
Secondary Structure
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:11336/48954
Acceder
id CONICETDig_992cc9bd9f558ef5d821e033a2d9ce85
oai_identifier_str oai:ri.conicet.gov.ar:11336/48954
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Structural remodeling during amyloidogenesis of physiological Nα-acetylated α-synucleinGallea, Jose IgnacioSarroukh, RabiaYunes Quartino, Pablo JavierRuysschaert, Jean-MarieRaussens, VincentCelej, Maria SoledadAcetylated-SynucleinAmyloidFibrillationFtirParkinson'S DiseaseSecondary Structurehttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The misfolding and aggregation of the presynaptic protein α-synuclein (AS) into amyloid fibrils is pathognomonic of Parkinson's disease, though the mechanism by which this structural conversion occurs is largely unknown. Soluble oligomeric species that accumulate as intermediates in the process of fibril formation are thought to be highly cytotoxic. Recent studies indicate that oligomer-to-fibril AS transition plays a key role in cell toxicity and progression of neurodegeneration. We previously demonstrated that a subgroup of oligomeric AS species are ordered assemblies possessing a well-defined pattern of intermolecular contacts which are arranged into a distinctive antiparallel β-sheet structure, as opposed to the parallel fibrillar fold. Recently, it was demonstrated that the physiological form of AS is N-terminally acetylated (Ac-AS). Here, we first showed that well-characterized conformational ensembles of Ac-AS, namely monomers, oligomers and fibrils, recapitulate many biophysical features of the nonacetylated protein, such as hydrodynamic, tinctorial, structural and membrane-leakage properties. Then, we relied on ATR-FTIR spectroscopy to explore the structural reorganization during Ac-AS fibrillogenesis. We found that antiparallel β-sheet transient intermediates are built-up at early stages of aggregation, which then evolve to parallel β-sheet fibrils through helix-rich/disordered species. The results are discussed in terms of regions of the protein that might participate in this structural rearrangement. Our work provides new insights into the complex conformational reorganization occurring during Ac-AS amyloid formation.Fil: Gallea, Jose Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; ArgentinaFil: Sarroukh, Rabia. Université Libre de Bruxelles; BélgicaFil: Yunes Quartino, Pablo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Ciencia y Tecnología de Alimentos Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Ciencia y Tecnología de Alimentos Córdoba; ArgentinaFil: Ruysschaert, Jean-Marie. Université Libre de Bruxelles; BélgicaFil: Raussens, Vincent. Université Libre de Bruxelles; BélgicaFil: Celej, Maria Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; ArgentinaElsevier Science2016-05info: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/11336/48954Gallea, Jose Ignacio; Sarroukh, Rabia; Yunes Quartino, Pablo Javier; Ruysschaert, Jean-Marie; Raussens, Vincent; et al.; Structural remodeling during amyloidogenesis of physiological Nα-acetylated α-synuclein; Elsevier Science; Biochimica Et Biophysica Acta-proteins And Proteomics; 1864; 5; 5-2016; 501-5101570-9639CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S1570963916300036info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bbapap.2016.01.011info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:49:31Zoai:ri.conicet.gov.ar:11336/48954instacron: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 09:49:31.897CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Structural remodeling during amyloidogenesis of physiological Nα-acetylated α-synuclein
title Structural remodeling during amyloidogenesis of physiological Nα-acetylated α-synuclein
spellingShingle Structural remodeling during amyloidogenesis of physiological Nα-acetylated α-synuclein
Gallea, Jose Ignacio
Acetylated-Synuclein
Amyloid
Fibrillation
Ftir
Parkinson'S Disease
Secondary Structure
title_short Structural remodeling during amyloidogenesis of physiological Nα-acetylated α-synuclein
title_full Structural remodeling during amyloidogenesis of physiological Nα-acetylated α-synuclein
title_fullStr Structural remodeling during amyloidogenesis of physiological Nα-acetylated α-synuclein
title_full_unstemmed Structural remodeling during amyloidogenesis of physiological Nα-acetylated α-synuclein
title_sort Structural remodeling during amyloidogenesis of physiological Nα-acetylated α-synuclein
dc.creator.none.fl_str_mv Gallea, Jose Ignacio
Sarroukh, Rabia
Yunes Quartino, Pablo Javier
Ruysschaert, Jean-Marie
Raussens, Vincent
Celej, Maria Soledad
author Gallea, Jose Ignacio
author_facet Gallea, Jose Ignacio
Sarroukh, Rabia
Yunes Quartino, Pablo Javier
Ruysschaert, Jean-Marie
Raussens, Vincent
Celej, Maria Soledad
author_role author
author2 Sarroukh, Rabia
Yunes Quartino, Pablo Javier
Ruysschaert, Jean-Marie
Raussens, Vincent
Celej, Maria Soledad
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Acetylated-Synuclein
Amyloid
Fibrillation
Ftir
Parkinson'S Disease
Secondary Structure
topic Acetylated-Synuclein
Amyloid
Fibrillation
Ftir
Parkinson'S Disease
Secondary Structure
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 misfolding and aggregation of the presynaptic protein α-synuclein (AS) into amyloid fibrils is pathognomonic of Parkinson's disease, though the mechanism by which this structural conversion occurs is largely unknown. Soluble oligomeric species that accumulate as intermediates in the process of fibril formation are thought to be highly cytotoxic. Recent studies indicate that oligomer-to-fibril AS transition plays a key role in cell toxicity and progression of neurodegeneration. We previously demonstrated that a subgroup of oligomeric AS species are ordered assemblies possessing a well-defined pattern of intermolecular contacts which are arranged into a distinctive antiparallel β-sheet structure, as opposed to the parallel fibrillar fold. Recently, it was demonstrated that the physiological form of AS is N-terminally acetylated (Ac-AS). Here, we first showed that well-characterized conformational ensembles of Ac-AS, namely monomers, oligomers and fibrils, recapitulate many biophysical features of the nonacetylated protein, such as hydrodynamic, tinctorial, structural and membrane-leakage properties. Then, we relied on ATR-FTIR spectroscopy to explore the structural reorganization during Ac-AS fibrillogenesis. We found that antiparallel β-sheet transient intermediates are built-up at early stages of aggregation, which then evolve to parallel β-sheet fibrils through helix-rich/disordered species. The results are discussed in terms of regions of the protein that might participate in this structural rearrangement. Our work provides new insights into the complex conformational reorganization occurring during Ac-AS amyloid formation.
Fil: Gallea, Jose Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina
Fil: Sarroukh, Rabia. Université Libre de Bruxelles; Bélgica
Fil: Yunes Quartino, Pablo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Ciencia y Tecnología de Alimentos Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Ciencia y Tecnología de Alimentos Córdoba; Argentina
Fil: Ruysschaert, Jean-Marie. Université Libre de Bruxelles; Bélgica
Fil: Raussens, Vincent. Université Libre de Bruxelles; Bélgica
Fil: Celej, Maria Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina
description The misfolding and aggregation of the presynaptic protein α-synuclein (AS) into amyloid fibrils is pathognomonic of Parkinson's disease, though the mechanism by which this structural conversion occurs is largely unknown. Soluble oligomeric species that accumulate as intermediates in the process of fibril formation are thought to be highly cytotoxic. Recent studies indicate that oligomer-to-fibril AS transition plays a key role in cell toxicity and progression of neurodegeneration. We previously demonstrated that a subgroup of oligomeric AS species are ordered assemblies possessing a well-defined pattern of intermolecular contacts which are arranged into a distinctive antiparallel β-sheet structure, as opposed to the parallel fibrillar fold. Recently, it was demonstrated that the physiological form of AS is N-terminally acetylated (Ac-AS). Here, we first showed that well-characterized conformational ensembles of Ac-AS, namely monomers, oligomers and fibrils, recapitulate many biophysical features of the nonacetylated protein, such as hydrodynamic, tinctorial, structural and membrane-leakage properties. Then, we relied on ATR-FTIR spectroscopy to explore the structural reorganization during Ac-AS fibrillogenesis. We found that antiparallel β-sheet transient intermediates are built-up at early stages of aggregation, which then evolve to parallel β-sheet fibrils through helix-rich/disordered species. The results are discussed in terms of regions of the protein that might participate in this structural rearrangement. Our work provides new insights into the complex conformational reorganization occurring during Ac-AS amyloid formation.
publishDate 2016
dc.date.none.fl_str_mv 2016-05
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/11336/48954
Gallea, Jose Ignacio; Sarroukh, Rabia; Yunes Quartino, Pablo Javier; Ruysschaert, Jean-Marie; Raussens, Vincent; et al.; Structural remodeling during amyloidogenesis of physiological Nα-acetylated α-synuclein; Elsevier Science; Biochimica Et Biophysica Acta-proteins And Proteomics; 1864; 5; 5-2016; 501-510
1570-9639
CONICET Digital
CONICET
url http://hdl.handle.net/11336/48954
identifier_str_mv Gallea, Jose Ignacio; Sarroukh, Rabia; Yunes Quartino, Pablo Javier; Ruysschaert, Jean-Marie; Raussens, Vincent; et al.; Structural remodeling during amyloidogenesis of physiological Nα-acetylated α-synuclein; Elsevier Science; Biochimica Et Biophysica Acta-proteins And Proteomics; 1864; 5; 5-2016; 501-510
1570-9639
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S1570963916300036
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bbapap.2016.01.011
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 Elsevier Science
publisher.none.fl_str_mv Elsevier 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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score 13.13397

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