WIPM OpenIR  > 磁共振基础研究部
Impact of the alpha-Synuclein Initial Ensemble Structure on Fibrillation Pathways and Kinetics
Bai, Jia1,2; Cheng, Kai1,2; Liu, Maili1; Li, Conggang1
2016-03-31
Source PublicationJOURNAL OF PHYSICAL CHEMISTRY B
Volume120Issue:12Pages:3140-3147
SubtypeArticle
AbstractThe presence of intracellular filamentous alpha-synuclein (alpha S) aggregates is a common feature in Parkinson's disease. Recombinant expressed and purified human alpha S is also capable of forming fibrils in vitro. Many studies have shown that solution conditions heavily influence alpha S fibrillation kinetics, fibril structure, and morphology that exhibit differential biological effects. Nevertheless, the alpha S ensemble structure in various solution conditions is not well characterized; furthermore, how the initial solution ensemble structures impact alpha S assembly kinetics and pathways that result in diverse fibril structure and morphology remains elusive. Here, we mainly employed NMR spectroscopy to characterize the initial ensemble structure of alpha S in the presence or absence of a 150 mM sodium chloride (NaCl) solution, where two polymorphs of alpha S were demonstrated in previous studies. Our data show that alpha S exhibits distinct conformations and fibrillation kinetics in these two solutions. alpha S adopts a more compact and rigid ensemble structure that has faster fibrillation kinetics in the absence of NaCl. On the basis of the ensemble structure and dynamics, we proposed a possible molecular mechanism in which alpha S forms different polymorphs under these two conditions. Our results provide novel insights into how the initial conformation impacts fibrillation pathways and kinetics, suggesting that a microenvironment can be used to regulate the intrinsically disordered proteins assembly.
WOS HeadingsScience & Technology ; Physical Sciences
DOI10.1021/acs.jpcb.6b01225
WOS KeywordNUCLEAR-MAGNETIC-RESONANCE ; PARKINSONS-DISEASE ; F-19 NMR ; LEWY BODIES ; AGGREGATION ; MUTATION ; FIBRILLIZATION ; ENHANCEMENT ; RESOLUTION ; COMPLEXES
Indexed BySCI
Language英语
WOS Research AreaChemistry
WOS SubjectChemistry, Physical
WOS IDWOS:000373416700015
Citation statistics
Document Type期刊论文
Identifierhttp://ir.wipm.ac.cn/handle/112942/9317
Collection磁共振基础研究部
Affiliation1.Chinese Acad Sci, Wuhan Inst Phys & Math, Natl Ctr Magnet Resonance Wuhan, Key Lab Magnet Resonance Biol Syst,State Key Lab, Wuhan 430071, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
Recommended Citation
GB/T 7714
Bai, Jia,Cheng, Kai,Liu, Maili,et al. Impact of the alpha-Synuclein Initial Ensemble Structure on Fibrillation Pathways and Kinetics[J]. JOURNAL OF PHYSICAL CHEMISTRY B,2016,120(12):3140-3147.
APA Bai, Jia,Cheng, Kai,Liu, Maili,&Li, Conggang.(2016).Impact of the alpha-Synuclein Initial Ensemble Structure on Fibrillation Pathways and Kinetics.JOURNAL OF PHYSICAL CHEMISTRY B,120(12),3140-3147.
MLA Bai, Jia,et al."Impact of the alpha-Synuclein Initial Ensemble Structure on Fibrillation Pathways and Kinetics".JOURNAL OF PHYSICAL CHEMISTRY B 120.12(2016):3140-3147.
Files in This Item:
There are no files associated with this item.
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Bai, Jia]'s Articles
[Cheng, Kai]'s Articles
[Liu, Maili]'s Articles
Baidu academic
Similar articles in Baidu academic
[Bai, Jia]'s Articles
[Cheng, Kai]'s Articles
[Liu, Maili]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Bai, Jia]'s Articles
[Cheng, Kai]'s Articles
[Liu, Maili]'s Articles
Terms of Use
No data!
Social Bookmark/Share
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.