Structured regions of α-synuclein fibrils include the early-onset Parkinson's disease mutation sites.
J Mol Biol
; 411(4): 881-95, 2011 Aug 26.
Article
em En
| MEDLINE
| ID: mdl-21718702
ABSTRACT
α-Synuclein (AS) fibrils are the major component of Lewy bodies, the pathological hallmark of Parkinson's disease (PD). Here, we use results from an extensive investigation employing solid-state NMR to present a detailed structural characterization and conformational dynamics quantification of full-length AS fibrils. Our results show that the core extends with a repeated structural motif. This result disagrees with the previously proposed fold of AS fibrils obtained with limited solid-state NMR data. Additionally, our results demonstrate that the three single point mutations associated with early-onset PD-A30P, E46K and A53T-are located in structured regions. We find that E46K and A53T mutations, located in rigid ß-strands of the wild-type fibrils, are associated with major and minor structural perturbations, respectively.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Parkinson
/
Corpos de Lewy
/
Mutação Puntual
/
Alfa-Sinucleína
Limite:
Humans
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article