Structural Identification of Individual Helical Amyloid Filaments by Integration of Cryo-Electron Microscopy-Derived Maps in Comparative Morphometric Atomic Force Microscopy Image Analysis.
Structural Identification of Individual Helical Amyloid Filaments by Integration of Cryo-Electron Microscopy-Derived Maps in Comparative Morphometric Atomic Force Microscopy Image Analysis.
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DOI：
10.1016/j.jmb.2022.167466
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发表时间：
2022-04-15
影响因子：
5.6
通讯作者：
Xue, Wei-Feng
中科院分区：
文献类型：
--
作者：
Lutter, Liisa;Al-Hilaly, Youssra K.;Serpell, Christopher J.;Tuite, Mick F.;Wischik, Claude M.;Serpell, Louise C.;Xue, Wei-Feng
淀粉样纤维的存在是50多种人类疾病的标志，包括神经退行性疾病和系统性淀粉样变性。理解淀粉样蛋白参与疾病的一个关键的未解决的挑战是解释淀粉样蛋白原纤维的个体结构多态性之间的关系，在潜在的混合人群中，与它们相关的特定病理学。虽然低温电子显微镜（cryo-EM）和固态核磁共振（ssNMR）光谱方法已成功地采用在最近几年来确定淀粉样蛋白原纤维的结构与高分辨率的细节，他们依赖于整体平均的原纤维结构在整个样品或显着的亚群。在这里，我们报告了一种方法，用于结构识别的个别原纤维结构的原子力显微镜（AFM）成像的高分辨率地图的淀粉样蛋白原纤维确定的冷冻EM在比较AFM图像分析的整合。使用迄今为止结构上未分辨的淀粉样原纤维证明了这种方法，所述淀粉样原纤维由tau（297-391）的片段（称为“dGAE”）在体外形成。我们的方法明确地建立了dGAE淀粉样蛋白原纤维与体外形成的肝素诱导的tau原纤维没有结构关系。此外，我们的比较分析导致预测dGAE原纤维在结构上密切相关的成对螺旋丝（PHF）分离自阿尔茨海默氏病（AD）脑组织的特征在于冷冻EM。这些结果显示了使用AFM的单个颗粒结构分析的实用性，提供了如何将冷冻EM数据纳入AFM图像分析的工作流程，并有助于淀粉样蛋白多态性的综合结构分析。
The presence of amyloid fibrils is a hallmark of more than 50 human disorders, including neurodegenerative diseases and systemic amyloidoses. A key unresolved challenge in understanding the involvement of amyloid in disease is to explain the relationship between individual structural polymorphs of amyloid fibrils, in potentially mixed populations, and the specific pathologies with which they are associated. Although cryo-electron microscopy (cryo-EM) and solid-state nuclear magnetic resonance (ssNMR) spectroscopy methods have been successfully employed in recent years to determine the structures of amyloid fibrils with high resolution detail, they rely on ensemble averaging of fibril structures in the entire sample or significant subpopulations. Here, we report a method for structural identification of individual fibril structures imaged by atomic force microscopy (AFM) by integration of high-resolution maps of amyloid fibrils determined by cryo-EM in comparative AFM image analysis. This approach was demonstrated using the hitherto structurally unresolved amyloid fibrils formed in vitro from a fragment of tau (297–391), termed ‘dGAE’. Our approach established unequivocally that dGAE amyloid fibrils bear no structural relationship to heparin-induced tau fibrils formed in vitro. Furthermore, our comparative analysis resulted in the prediction that dGAE fibrils are structurally closely related to the paired helical filaments (PHFs) isolated from Alzheimer’s disease (AD) brain tissue characterised by cryo-EM. These results show the utility of individual particle structural analysis using AFM, provide a workflow of how cryo-EM data can be incorporated into AFM image analysis and facilitate an integrated structural analysis of amyloid polymorphism.
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DOI：
10.1126/science.aao2825
发表时间：
2017-10-06
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gremer L;Schölzel D;Schenk C;Reinartz E;Labahn J;Ravelli RBG;Tusche M;Lopez-Iglesias C;Hoyer W;Heise H;Willbold D;Schröder GF
通讯作者：
Schröder GF
影响因子：
16.6
作者：
Pyne ALB;Noy A;Main KHS;Velasco-Berrelleza V;Piperakis MM;Mitchenall LA;Cugliandolo FM;Beton JG;Stevenson CEM;Hoogenboom BW;Bates AD;Maxwell A;Harris SA
通讯作者：
Harris SA
影响因子：
--
作者：
Lutter, Liisa;Serpell, Christopher;Xue, Wei-Feng
通讯作者：
Xue, Wei-Feng
影响因子：
16.6
作者：
Ruggeri FS;Longo G;Faggiano S;Lipiec E;Pastore A;Dietler G
通讯作者：
Dietler G
DOI：
10.1073/pnas.2104148118
发表时间：
2021-09-07
影响因子：
11.1
作者：
Koloteva-Levine N;Aubrey LD;Marchante R;Purton TJ;Hiscock JR;Tuite MF;Xue WF
通讯作者：
Xue WF