Artículo
Small-Molecule-Induced Soluble Oligomers of α-Synuclein with Helical Structure
Fonseca Ornelas, Luis; Schmidt, Carla; Camacho Zarco, Aldo R.; Fernandez, Claudio Oscar
; Becker, Stefan; Zweckstetter, Markus
Fecha de publicación:
09/2017
Editorial:
Wiley VCH Verlag
Revista:
Chemistry- A European Journal
ISSN:
0947-6539
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Accumulation of α-synuclein (αSyn) aggregates constitutes the hallmark of synucleinopathies including Parkinson's disease. However, many steps from the innocuous, monomeric αSyn toward misfolded oligomers and fibrillar species remain unclear. Here, we show that αSyn can form in solution α-helical oligomers, which are off-pathway to fibrillization, through interaction with the tetrapyrrole phthalocyanine tetrasulfonate. Chemical cross-linking combined with mass spectrometry reveals a large number of intermolecular cross-links along the entire αSyn sequence in the phthalocyanine tetrasulfonate-stabilized αSyn oligomers. Our study suggests that stabilization of structured oligomers by small molecules provides a viable strategy to interfere with αSyn fibrillization.
Palabras clave:
Alpha-Synuclein
,
Mass Spectrometry
,
Oligomers
,
Polymerization
,
Proteins
Archivos asociados
Licencia
Identificadores
Colecciones
Articulos(CCT - ROSARIO)
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - ROSARIO
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - ROSARIO
Citación
Fonseca Ornelas, Luis; Schmidt, Carla; Camacho Zarco, Aldo R.; Fernandez, Claudio Oscar; Becker, Stefan; et al.; Small-Molecule-Induced Soluble Oligomers of α-Synuclein with Helical Structure; Wiley VCH Verlag; Chemistry- A European Journal; 23; 53; 9-2017; 13010-13014
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