期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 291, 期 43, 页码 22618-22629出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M116.739250
关键词
-synuclein (a-synuclein); amyloid; analytical ultracentrifugation; fibril; molecular chaperone; Parkinson disease; protein aggregation; small heat shock protein (sHsp); synuclein
资金
- Australian Department of Health and Aging
- University of Wollongong
- Australian Postgraduate Award
- Australian Research Council [FT110100586, FT140100544]
- Australian National Health and Medical Research Council [1068087]
- National Health and Medical Research Council of Australia [1068087] Funding Source: NHMRC
- Australian Research Council [FT110100586, FT140100544] Funding Source: Australian Research Council
The aggregation of -synuclein (-syn) into amyloid fibrils is associated with neurodegenerative diseases, collectively referred to as the -synucleinopathies. In vivo, molecular chaperones, such as the small heat-shock proteins (sHsps), normally act to prevent protein aggregation; however, it remains to be determined how aggregation-prone -syn evades sHsp chaperone action leading to its disease-associated deposition. This work examines the molecular mechanism by which two canonical sHsps, B-crystallin (B-c) and Hsp27, interact with aggregation-prone -syn to prevent its aggregation in vitro. Both sHsps are very effective inhibitors of -syn aggregation, but no stable complex between the sHsps and -syn was detected, indicating that the sHsps inhibit -syn aggregation via transient interactions. Moreover, the ability of these sHsps to prevent -syn aggregation was dependent on the kinetics of aggregation; the faster the rate of aggregation (shorter the lag phase), the less effective the sHsps were at inhibiting fibril formation of -syn. Thus, these findings indicate that the rate at which -syn aggregates in cells may be a significant factor in how it evades sHsp chaperone action in the -synucleinopathies.
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