Role of Tyr-39 for the Structural Features of α-Synuclein and for the Interaction with a Strong Modulator of Its Amyloid Assembly
- Autores
- Palomino Hernandez, Oscar; Buratti, Fiamma Ayelen; Sacco, Pamela Soledad; Rossetti, Giulia; Carloni, Paolo; Fernandez, Claudio Oscar
- Año de publicación
- 2020
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Recent studies suggest that Tyr-39 might play a critical role for both the normal function and the pathological dysfunction of α-synuclein (αS), an intrinsically disordered protein involved in Parkinson’s disease. We perform here a comparative analysis between the structural features of human αS and its Y39A, Y39F, and Y39L variants. By the combined application of site-directed mutagenesis, biophysical techniques, and enhanced sampling molecular simulations, we show that removing aromatic functionality at position 39 of monomeric αS leads to protein variants populating more compact conformations, conserving its disordered nature and secondary structure propensities. Contrasting with the subtle changes induced by mutations on the protein structure, removing aromaticity at position 39 impacts strongly on the interaction of αS with the potent amyloid inhibitor phthalocyanine tetrasulfonate (PcTS). Our findings further support the role of Tyr-39 in forming essential inter and intramolecular contacts that might have important repercussions for the function and the dysfunction of αS.
Fil: Palomino Hernandez, Oscar. The Hebrew University of Jerusalem; Israel
Fil: Buratti, Fiamma Ayelen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario. Universidad Nacional de Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario; Argentina
Fil: Sacco, Pamela Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario. Universidad Nacional de Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario; Argentina
Fil: Rossetti, Giulia. No especifíca;
Fil: Carloni, Paolo. No especifíca;
Fil: Fernandez, Claudio Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario. Universidad Nacional de Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario; Argentina - Materia
-
ALPHA SYNUCLEIN
MUTAGENESIS
AROMATICITY
AGGREGATION - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/257780
Ver los metadatos del registro completo
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CONICET Digital (CONICET) |
spelling |
Role of Tyr-39 for the Structural Features of α-Synuclein and for the Interaction with a Strong Modulator of Its Amyloid AssemblyPalomino Hernandez, OscarBuratti, Fiamma AyelenSacco, Pamela SoledadRossetti, GiuliaCarloni, PaoloFernandez, Claudio OscarALPHA SYNUCLEINMUTAGENESISAROMATICITYAGGREGATIONhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Recent studies suggest that Tyr-39 might play a critical role for both the normal function and the pathological dysfunction of α-synuclein (αS), an intrinsically disordered protein involved in Parkinson’s disease. We perform here a comparative analysis between the structural features of human αS and its Y39A, Y39F, and Y39L variants. By the combined application of site-directed mutagenesis, biophysical techniques, and enhanced sampling molecular simulations, we show that removing aromatic functionality at position 39 of monomeric αS leads to protein variants populating more compact conformations, conserving its disordered nature and secondary structure propensities. Contrasting with the subtle changes induced by mutations on the protein structure, removing aromaticity at position 39 impacts strongly on the interaction of αS with the potent amyloid inhibitor phthalocyanine tetrasulfonate (PcTS). Our findings further support the role of Tyr-39 in forming essential inter and intramolecular contacts that might have important repercussions for the function and the dysfunction of αS.Fil: Palomino Hernandez, Oscar. The Hebrew University of Jerusalem; IsraelFil: Buratti, Fiamma Ayelen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario. Universidad Nacional de Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario; ArgentinaFil: Sacco, Pamela Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario. Universidad Nacional de Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario; ArgentinaFil: Rossetti, Giulia. No especifíca;Fil: Carloni, Paolo. No especifíca;Fil: Fernandez, Claudio Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario. Universidad Nacional de Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario; ArgentinaMolecular Diversity Preservation International2020-07info: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/11336/257780Palomino Hernandez, Oscar; Buratti, Fiamma Ayelen; Sacco, Pamela Soledad; Rossetti, Giulia; Carloni, Paolo; et al.; Role of Tyr-39 for the Structural Features of α-Synuclein and for the Interaction with a Strong Modulator of Its Amyloid Assembly; Molecular Diversity Preservation International; International Journal of Molecular Sciences; 21; 14; 7-2020; 1-151422-0067CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/1422-0067/21/14/5061info:eu-repo/semantics/altIdentifier/doi/10.3390/ijms21145061info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:10:39Zoai:ri.conicet.gov.ar:11336/257780instacron: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 10:10:40.154CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Role of Tyr-39 for the Structural Features of α-Synuclein and for the Interaction with a Strong Modulator of Its Amyloid Assembly |
title |
Role of Tyr-39 for the Structural Features of α-Synuclein and for the Interaction with a Strong Modulator of Its Amyloid Assembly |
spellingShingle |
Role of Tyr-39 for the Structural Features of α-Synuclein and for the Interaction with a Strong Modulator of Its Amyloid Assembly Palomino Hernandez, Oscar ALPHA SYNUCLEIN MUTAGENESIS AROMATICITY AGGREGATION |
title_short |
Role of Tyr-39 for the Structural Features of α-Synuclein and for the Interaction with a Strong Modulator of Its Amyloid Assembly |
title_full |
Role of Tyr-39 for the Structural Features of α-Synuclein and for the Interaction with a Strong Modulator of Its Amyloid Assembly |
title_fullStr |
Role of Tyr-39 for the Structural Features of α-Synuclein and for the Interaction with a Strong Modulator of Its Amyloid Assembly |
title_full_unstemmed |
Role of Tyr-39 for the Structural Features of α-Synuclein and for the Interaction with a Strong Modulator of Its Amyloid Assembly |
title_sort |
Role of Tyr-39 for the Structural Features of α-Synuclein and for the Interaction with a Strong Modulator of Its Amyloid Assembly |
dc.creator.none.fl_str_mv |
Palomino Hernandez, Oscar Buratti, Fiamma Ayelen Sacco, Pamela Soledad Rossetti, Giulia Carloni, Paolo Fernandez, Claudio Oscar |
author |
Palomino Hernandez, Oscar |
author_facet |
Palomino Hernandez, Oscar Buratti, Fiamma Ayelen Sacco, Pamela Soledad Rossetti, Giulia Carloni, Paolo Fernandez, Claudio Oscar |
author_role |
author |
author2 |
Buratti, Fiamma Ayelen Sacco, Pamela Soledad Rossetti, Giulia Carloni, Paolo Fernandez, Claudio Oscar |
author2_role |
author author author author author |
dc.subject.none.fl_str_mv |
ALPHA SYNUCLEIN MUTAGENESIS AROMATICITY AGGREGATION |
topic |
ALPHA SYNUCLEIN MUTAGENESIS AROMATICITY AGGREGATION |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
dc.description.none.fl_txt_mv |
Recent studies suggest that Tyr-39 might play a critical role for both the normal function and the pathological dysfunction of α-synuclein (αS), an intrinsically disordered protein involved in Parkinson’s disease. We perform here a comparative analysis between the structural features of human αS and its Y39A, Y39F, and Y39L variants. By the combined application of site-directed mutagenesis, biophysical techniques, and enhanced sampling molecular simulations, we show that removing aromatic functionality at position 39 of monomeric αS leads to protein variants populating more compact conformations, conserving its disordered nature and secondary structure propensities. Contrasting with the subtle changes induced by mutations on the protein structure, removing aromaticity at position 39 impacts strongly on the interaction of αS with the potent amyloid inhibitor phthalocyanine tetrasulfonate (PcTS). Our findings further support the role of Tyr-39 in forming essential inter and intramolecular contacts that might have important repercussions for the function and the dysfunction of αS. Fil: Palomino Hernandez, Oscar. The Hebrew University of Jerusalem; Israel Fil: Buratti, Fiamma Ayelen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario. Universidad Nacional de Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario; Argentina Fil: Sacco, Pamela Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario. Universidad Nacional de Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario; Argentina Fil: Rossetti, Giulia. No especifíca; Fil: Carloni, Paolo. No especifíca; Fil: Fernandez, Claudio Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario. Universidad Nacional de Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario; Argentina |
description |
Recent studies suggest that Tyr-39 might play a critical role for both the normal function and the pathological dysfunction of α-synuclein (αS), an intrinsically disordered protein involved in Parkinson’s disease. We perform here a comparative analysis between the structural features of human αS and its Y39A, Y39F, and Y39L variants. By the combined application of site-directed mutagenesis, biophysical techniques, and enhanced sampling molecular simulations, we show that removing aromatic functionality at position 39 of monomeric αS leads to protein variants populating more compact conformations, conserving its disordered nature and secondary structure propensities. Contrasting with the subtle changes induced by mutations on the protein structure, removing aromaticity at position 39 impacts strongly on the interaction of αS with the potent amyloid inhibitor phthalocyanine tetrasulfonate (PcTS). Our findings further support the role of Tyr-39 in forming essential inter and intramolecular contacts that might have important repercussions for the function and the dysfunction of αS. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-07 |
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/11336/257780 Palomino Hernandez, Oscar; Buratti, Fiamma Ayelen; Sacco, Pamela Soledad; Rossetti, Giulia; Carloni, Paolo; et al.; Role of Tyr-39 for the Structural Features of α-Synuclein and for the Interaction with a Strong Modulator of Its Amyloid Assembly; Molecular Diversity Preservation International; International Journal of Molecular Sciences; 21; 14; 7-2020; 1-15 1422-0067 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/257780 |
identifier_str_mv |
Palomino Hernandez, Oscar; Buratti, Fiamma Ayelen; Sacco, Pamela Soledad; Rossetti, Giulia; Carloni, Paolo; et al.; Role of Tyr-39 for the Structural Features of α-Synuclein and for the Interaction with a Strong Modulator of Its Amyloid Assembly; Molecular Diversity Preservation International; International Journal of Molecular Sciences; 21; 14; 7-2020; 1-15 1422-0067 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.mdpi.com/1422-0067/21/14/5061 info:eu-repo/semantics/altIdentifier/doi/10.3390/ijms21145061 |
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 |
Molecular Diversity Preservation International |
publisher.none.fl_str_mv |
Molecular Diversity Preservation International |
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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1842270129052712960 |
score |
13.13397 |