Amyloid Fibril Polymorphism: Almost Identical on the Atomic Level, Mesoscopically Very Different
Amyloid Fibril Polymorphism: Almost Identical on the Atomic Level, Mesoscopically Very Different
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DOI：
10.1021/acs.jpcb.6b10624
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发表时间：
2017-03-02
影响因子：
3.3
通讯作者：
Riek, Roland
中科院分区：
文献类型：
--
作者：
Seuring, Carolin;Verasdonck, Joeri;Riek, Roland
通过负染色透射电子显微镜、扫描透射电子显微镜和固态核磁共振波谱研究了扭曲和直β-内啡肽原纤维的淀粉样蛋白多态性。在有盐存在的情况下，原纤维聚集形成扁平的条纹带，而在没有盐的情况下，它们主要形成扭曲的细丝。为了深入了解它们在原子水平上的结构差异，获得了两种原纤维类型的 3D 固态 NMR 光谱，从而可以检测两种制剂中 C-13 和 N-15 原子化学位移的差异。两种原纤维类型的光谱指纹和化学位移非常相似。这表明单体结构和分子界面几乎相同，但这些微小的差异确实会传播以在介观尺度上产生平坦和扭曲的形态。这一发现与不同盐条件下聚合物（包括淀粉样蛋白）组装的实验和理论考虑相一致，将扁平原纤维与扭曲原纤维的介观差异归因于静电分子间排斥力。
Amyloid polymorphism of twisted and straight beta-endorphin fibrils was studied by negative-stain transmission electron microscopy, scanning transmission electron microscopy, and solid-state nuclear magnetic resonance spectroscopy. Whereas fibrils assembled in the presence of salt formed flat, striated ribbons, in the absence of salt they formed mainly twisted filaments. To get insights into their structural differences at the atomic level, 3D solid-state NMR spectra of both fibril types were acquired, allowing the detection of the differences in chemical shifts of C-13 and N-15 atoms in both preparations. The spectral fingerprints and therefore the chemical shifts are very similar for both fibril types. This indicates that the monomer structure and the molecular interfaces are almost the same but that these small differences do propagate to produce flat and twisted morphologies at the mesoscopic scale. This finding is in agreement with both experimental and theoretical considerations on the assembly of polymers (including amyloids) under different salt conditions, which attribute the mesoscopic difference of flat versus twisted fibrils to electrostatic intermolecular repulsions.