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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通过纳米形态测量法对淀粉样蛋白原纤维多态性进行定量揭示了丝组装的个体性
DOI：
10.1101/2020.01.14.905877
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Aubrey L
中科院分区：
文献类型：
--
作者：
Aubrey L
淀粉样原纤维是由许多不同蛋白质形成的高度多态性结构。它们提供生物功能，但也在许多人类疾病中异常积累。淀粉样蛋白多态性的物理化学原理不被理解，由于缺乏在单纤维水平的结构见解。识别和分类不同的纤维多晶型物并量化异质性水平对于解读淀粉样蛋白结构与其功能和疾病相关性质（如毒性、菌株、繁殖和扩散）之间的精确联系至关重要。采用温和的，力距离曲线为基础的原子力显微镜，我们产生详细的图像，从其中的3D重建的个别丝在异质性淀粉样蛋白样品实现。然后通过层次聚类对不同的原纤维多晶型物进行分类，并客观地量化样品异质性。这些数据表明，原纤维人口的多态性，提供了重要的信息，淀粉样蛋白自组装的能量景观，并提供定量的见解淀粉样蛋白人口的多态性的结构基础。
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.
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