Quantification of amyloid fibril polymorphism by nano-morphometry reveals the individuality of filament assembly.
Quantification of amyloid fibril polymorphism by nano-morphometry reveals the individuality of filament assembly.
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DOI：
10.1038/s42004-020-00372-3
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发表时间：
2020-09-11
影响因子：
5.9
通讯作者：
Xue, Wei-Feng
中科院分区：
文献类型：
--
作者：
Aubrey, Liam D.;Blakeman, Ben J. F.;Lutter, Liisa;Serpell, Christopher J.;Tuite, Mick F.;Serpell, Louise C.;Xue, Wei-Feng
淀粉样纤维是由许多不同的蛋白质组成的高度多态的结构。它们提供生物功能，但也会在许多人类疾病中异常积累。由于缺乏单纤维水平的结构洞察，淀粉样蛋白多态的物理化学原理尚不清楚。对不同的纤维多态进行鉴定和分类，并量化其异质性水平，对于破译淀粉样蛋白结构与其功能和疾病相关特性(如毒性、菌株、繁殖和传播)之间的精确联系至关重要。使用温和的、基于力-距离曲线的原子力显微镜，我们产生了详细的图像，从这些图像中，我们实现了对非均质淀粉样蛋白样本中单个细丝的三维重建。然后通过系统聚类对不同的纤维多形性进行分类，并客观地量化样品的异质性。这些数据显示了原纤维种群的多态性质，提供了有关淀粉样蛋白自组装的能量格局的重要信息，并提供了对淀粉样蛋白种群多态的结构基础的定量见解。单一的淀粉样蛋白或多肽可以采用许多不同的纤维3D结构，但这种多态现象却鲜为人知。在这里，详细的AFM成像允许重建单个纤维的3D模型，这些模型可以根据其单独的结构属性进行聚集。
Amyloid fibrils are highly polymorphic structures formed by many different proteins. They provide biological function but also abnormally accumulate in numerous human diseases. The physicochemical principles of amyloid polymorphism are not understood due to lack of structural insights at the single-fibril level. To identify and classify different fibril polymorphs and to quantify the level of heterogeneity is essential to decipher the precise links between amyloid structures and their functional and disease associated properties such as toxicity, strains, propagation and spreading. Employing gentle, force-distance curve-based AFM, we produce detailed images, from which the 3D reconstruction of individual filaments in heterogeneous amyloid samples is achieved. Distinctive fibril polymorphs are then classified by hierarchical clustering, and sample heterogeneity is objectively quantified. These data demonstrate the polymorphic nature of fibril populations, provide important information regarding the energy landscape of amyloid self-assembly, and offer quantitative insights into the structural basis of polymorphism in amyloid populations. A single amyloid-forming protein or peptide can adopt many different fibrillar 3D structures, but this polymorphism is poorly understood. Here, detailed AFM imaging allows for the reconstruction of 3D models of individual fibrils which can be clustered on the basis of their individual structural properties.
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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：
3.4
作者：
Berryman, Joshua T.;Radford, Sheena E.;Harris, Sarah A.
通讯作者：
Harris, Sarah A.
影响因子：
3.4
作者：
Hill, Shannon E.;Robinson, Joshua;Muschol, Martin
通讯作者：
Muschol, Martin
DOI：
10.1073/pnas.1218402110
发表时间：
2013-06-11
影响因子：
11.1
作者：
Cohen, Samuel I. A.;Linse, Sara;Knowles, Tuomas P. J.
通讯作者：
Knowles, Tuomas P. J.
影响因子：
2.3
作者：
Cohen, Mark;Appleby, Brian;Safar, Jiri G.
通讯作者：
Safar, Jiri G.