Impact of the alpha-Synuclein Initial Ensemble Structure on Fibrillation Pathways and Kinetics
文献类型：期刊论文
| 作者 | Bai, Jia1,2; Cheng, Kai1,2; Liu, Maili1; Li, Conggang1 |
| 刊名 | JOURNAL OF PHYSICAL CHEMISTRY B
 |
| 出版日期 | 2016-03-31 |
| 卷号 | 120期号:12页码:3140-3147 |
| 英文摘要 | The 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标题词 | Science & Technology ; Physical Sciences |
| 类目[WOS] | Chemistry, Physical |
| 研究领域[WOS] | Chemistry |
| 关键词[WOS] | NUCLEAR-MAGNETIC-RESONANCE ; PARKINSONS-DISEASE ; F-19 NMR ; LEWY BODIES ; AGGREGATION ; MUTATION ; FIBRILLIZATION ; ENHANCEMENT ; RESOLUTION ; COMPLEXES |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000373416700015 |
| 源URL | [http://ir.wipm.ac.cn/handle/112942/9317]  |
| 专题 | 武汉物理与数学研究所_磁共振基础研究部 |
| 作者单位 | 1.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 |
| 推荐引用方式 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. |
入库方式： OAI收割
来源：武汉物理与数学研究所
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