期刊
ACS NANO
卷 14, 期 5, 页码 5213-5222出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.9b09676
关键词
neurodegenerative disorders; protein misfolding; single-molecule biophysics; atomic force microscopy; infrared spectroscopy
类别
资金
- Boehringer Ingelheim Fonds
- German National Merit Foundation
- Swiss National Science Foundation
- Darwin College
- UK Biotechnology and Biochemical Sciences Research Council
- Wellcome Trust
- Frances and Augustus Newman Foundation
- Cambridge Centre for Misfolding Diseases
Proteinaceous deposits of alpha-synuclein amyloid fibrils are a hallmark of human disorders including Parkinson's disease. The onset of this disease is also associated with five familial mutations of the gene encoding the protein. However, the mechanistic link between single point mutations and the kinetics of aggregation, biophysical properties of the resulting amyloid fibrils, and an increased risk of disease is still elusive. Here, we demonstrate that the disease-associated mutations of alpha-synuclein generate different amyloid fibril polymorphs compared to the wild type protein. Remarkably, the alpha-synuclein variants forming amyloid fibrils of a comparable structure, morphology, and heterogeneity show similar microscopic steps defining the aggregation kinetics. These results demonstrate that a single point mutation can significantly alter the distribution of fibrillar polymorphs in alpha-synuclein, suggesting that differences in the clinical phenotypes of familial Parkinson's disease could be associated with differences in the mechanism of formation and the structural characteristics of the aggregates.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据