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DOI | 10.1175/JCLI-D-19-0077.1 |
Single-vesicle imaging reveals lipid-selective and stepwise membrane disruption by monomeric alpha-synuclein | |
Hannestad, Jonas K.1; Rocha, Sandra2; Agnarsson, Bjorn1; Zhdanov, Vladimir P.1,3; Wittung-Stafshede, Pernilla2; Hook, Fredrik1 | |
2019-12-01 | |
发表期刊 | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
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ISSN | 0027-8424 |
出版年 | 2020 |
卷号 | 117期号:25页码:14178-14186 |
文章类型 | Article |
语种 | 英语 |
国家 | Sweden; Russia |
英文摘要 | The interaction of the neuronal protein alpha-synuclein with lipid membranes appears crucial in the context of Parkinson's disease, but the underlying mechanistic details, including the roles of different lipids in pathogenic protein aggregation and membrane disruption, remain elusive. Here, we used single-vesicle resolution fluorescence and label-free scattering microscopy to investigate the interaction kinetics of monomeric alpha-synuclein with surface-tethered vesicles composed of different negatively charged lipids. Supported by a theoretical model to account for structural changes in scattering properties of surface-tethered lipid vesicles, the data demonstrate stepwise vesicle disruption and asymmetric membrane deformation upon alpha-synuclein binding to phosphatidylglycerol vesicles at protein concentrations down to 10 nM (similar to 100 proteins per vesicle). In contrast, phosphatidylserine vesicles were only marginally affected. These insights into structural consequences of alpha-synuclein interaction with lipid vesicles highlight the contrasting roles of different anionic lipids, which may be of mechanistic relevance for both normal protein function (e.g., synaptic vesicle binding) and dysfunction (e.g., mitochondrial membrane interaction). |
英文关键词 | alpha-synuclein single-vesicle scattering lipid vesicle membrane interaction |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000546772500020 |
WOS关键词 | SURFACE-PLASMON RESONANCE ; PARKINSONS-DISEASE ; PACKING DEFECTS ; PROTEIN ; MECHANISM ; BINDING ; CURVATURE ; PERMEABILIZATION ; QUANTIFICATION ; FIBRILLIZATION |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/225631 |
专题 | 环境与发展全球科技态势 |
作者单位 | 1.Chalmers Univ Technol, Dept Phys, Div Nano & Biol Phys, S-41296 Gothenburg, Sweden; 2.Chalmers Univ Technol, Dept Biol & Biol Engn, Div Chem Biol, S-41296 Gothenburg, Sweden; 3.Russian Acad Sci, Boreskov Inst Catalysis, Novosibirsk 630090, Russia |
推荐引用方式 GB/T 7714 | Hannestad, Jonas K.,Rocha, Sandra,Agnarsson, Bjorn,et al. Single-vesicle imaging reveals lipid-selective and stepwise membrane disruption by monomeric alpha-synuclein[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2019,117(25):14178-14186. |
APA | Hannestad, Jonas K.,Rocha, Sandra,Agnarsson, Bjorn,Zhdanov, Vladimir P.,Wittung-Stafshede, Pernilla,&Hook, Fredrik.(2019).Single-vesicle imaging reveals lipid-selective and stepwise membrane disruption by monomeric alpha-synuclein.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,117(25),14178-14186. |
MLA | Hannestad, Jonas K.,et al."Single-vesicle imaging reveals lipid-selective and stepwise membrane disruption by monomeric alpha-synuclein".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 117.25(2019):14178-14186. |
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