Título:
Revisiting the role of 3-nitrotyrosine residues in the formation of alpha-synuclein oligomers and fibrils
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Autor:
Chavarría, Cecilia
Ivagnes, Rodrigo
Zeida, Ari
Piñeyro, María Dolores
Souza, José M.
Ivagnes, Rodrigo
Zeida, Ari
Piñeyro, María Dolores
Souza, José M.
Tutor:
Tipo de documento:
Preprint
Editor:
Palabras clave:
Alpha-synuclein
Post-translational modification
3-nitrotyrosine
Fibrils
Oligomers
Post-translational modification
3-nitrotyrosine
Fibrils
Oligomers
Descriptores:
NITRATOS
METABOLISMO
ENFERMEDAD DE PARKINSON
SINUCLEINOPATÍAS
TIROSINA
ALFA-SINUCLEÍNA
METABOLISMO
ENFERMEDAD DE PARKINSON
SINUCLEINOPATÍAS
TIROSINA
ALFA-SINUCLEÍNA
Año de publicación:
2024
Contenido:
Resumen:
Nitration of tyrosine residues in alpha-synuclein (a-syn) has been detected in different synucleinopathies, including Parkinson’s disease. The potential role of 3-nitrotyrosine formation in a-syn, as an oxidative post- translational modification, is still elusive. In this work, we generated well-characterized tyrosine nitrated a- syn monomers and studied their capability to form oligomers and fibrils. We constructed tyrosine to phenylalanine mutants, containing a single tyrosine residue, a-syn mutant Y(125/133/136)F and Y(39/125/133)F) and assessed the impact in a-syn biophysical properties. Nitrated wild-type a-syn and the Y–F mutants, with one 3- nitrotyrosine residue in either the protein’s N-terminal or C-terminal region, showed inhibition of fibril formation but retained the capacity of oligomer formation. The inhibition of a-syn fibrillation occurs even when an important amount of unmodified a-syn is still present. We characterized oligomers from both nitrated and non- nitrated forms of the wild-type protein and the mutant forms obtained. Our results indicate that the formation of 3-nitrotyrosine in a-syn could induce an off-pathway oligomer formation which may have an important impact in the development of synucleinopathies.
Descripción:
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Elsevier
EN:
Archives of Biochemistry and Biophysics. 2024;752
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Citación:
Chavarría C, Ivagnes R, Zeida A y otros. Revisiting the role of 3-nitrotyrosine residues in the formation of alpha-synuclein oligomers and fibrils [Preprint] Publicado en Archives of Biochemistry and Biophysics 2024;752.10 p.
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Licencia Creative Commons Atribución - No Comercial (CC - By-NC 4.0)
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| Ficheros | Descripción | Tamaño | Formato | ||
|---|---|---|---|---|---|
| Revisiting the role of 3-nitrotyrosine residues in the formation of alpha-synuclein oligomers and fibrils (Accepted version) (1).pdf | — | 1.2 MB | Adobe PDF |