Temperature-dependent structural changes of Parkinson's alpha-synuclein reveal the role of pre-existing oligomers in alpha-synuclein fibrillization.
Related Articles Temperature-dependent structural changes of Parkinson's alpha-synuclein reveal the role of pre-existing oligomers in alpha-synuclein fibrillization.
PLoS One. 2013;8(1):e53487
Authors: Ariesandi W, Chang CF, Chen TE, Chen YR
Abstract
Amyloid fibrils of ?-synuclein are the main constituent of Lewy bodies deposited in substantial nigra of Parkinson's disease brains. ?-Synuclein is an intrinsically disordered protein lacking compact secondary and tertiary structures. To enhance the understanding of its structure and function relationship, we utilized temperature treatment to study ?-synuclein conformational changes and the subsequent effects. We found that after 1 hr of high temperature pretreatment, >80°C, ?-synuclein fibrillization was significantly inhibited. However, the temperature melting coupled with circular dichroism spectra showed that ?-synuclein was fully reversible and the NMR studies showed no observable structural changes of ?-synuclein after 95°C treatment. By using cross-linking and analytical ultracentrifugation, rare amount of pre-existing ?-synuclein oligomers were found to decrease after the high temperature treatment. In addition, a small portion of C-terminal truncation of ?-synuclein also occurred. The reduction of pre-existing oligomers of ?-synuclein may contribute to less seeding effect that retards the kinetics of amyloid fibrillization. Overall, our results showed that the pre-existing oligomeric species is a key factor contributing to ?-synuclein fibrillization. Our results facilitate the understanding of ?-synuclein fibrillization.
PMID: 23349712 [PubMed - in process]
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