The effect of tyrosine residues on α-synuclein fibrillation.
Acta Chim Slov
; 62(1): 181-9, 2015.
Article
em En
| MEDLINE
| ID: mdl-25830974
ABSTRACT
Aggregation of the intrinsically disordered protein α-synuclein into ordered amyloid fibrils is implicated in the pathogenesis of Parkinson's disease. To unravel the role of Tyr residues in α-synuclein fibrillation, we prepared recombinant N-terminal (Y39A) and C-terminal (Y(125,133,136)A) mutants of α-synuclein and examined their fibrillation propensities by thioflavin T and 1-anilinonaphthalene-8-sulfonate (ANS) fluorescent probes, SDS-PAGE and atomic force microscopy. We demonstrate that in contrast to wild-type α-synuclein, both mutants show large, but comparable delays in the fibrillation process and exhibit enhanced hydrophobicity during fibril-like assembly. Both Tyr mutants form fibril-like structures after prolonged incubation periods, which are morphologically distinct from those of the wild-type protein. Our results suggest that the N-terminal and C-terminal Tyr residues of α-synuclein are important primarily for the initiation of the fibrillation process.
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Base de dados:
MEDLINE
Assunto principal:
Tirosina
/
Alfa-Sinucleína
Limite:
Humans
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article