Cryo-EM fibril structures from systemic AA amyloidosis reveal the species complementarity of pathological amyloids
Cryo-EM fibril structures from systemic AA amyloidosis reveal the species complementarity of pathological amyloids
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DOI：
10.1038/s41467-019-09033-z
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发表时间：
2019-03-07
影响因子：
16.6
通讯作者：
Schmidt, Matthias
中科院分区：
文献类型：
--
作者：
Liberta, Falk;Loerch, Sarah;Schmidt, Matthias
系统性AA淀粉样变性是一种世界性的蛋白质错误折叠疾病。它是由急性期蛋白血清淀粉样蛋白A形成淀粉样纤维引起的。在这里，我们报告的纯化和电子冷冻显微镜分析的淀粉样纤维从小鼠和人类患者的系统性AA淀粉样变性。对于鼠和人原纤维，获得的分辨率分别为3.0埃和2.7埃。这两种原纤维的基本性质不同，例如存在右旋或左旋扭曲的交叉β折叠和原纤维蛋白的整体折叠。然而，这两种蛋白质在N-末端内采用高度相似的β-拱形构象，类似于21个残基。我们的数据表明的重要性的原纤维蛋白N-末端的稳定性分析的淀粉样蛋白原纤维形态和建议的战略，打击这种疾病的干扰与特定的原纤维多态性。
Systemic AA amyloidosis is a worldwide occurring protein misfolding disease of humans and animals. It arises from the formation of amyloid fibrils from the acute phase protein serum amyloid A. Here, we report the purification and electron cryo-microscopy analysis of amyloid fibrils from a mouse and a human patient with systemic AA amyloidosis. The obtained resolutions are 3.0 angstrom and 2.7 angstrom for the murine and human fibril, respectively. The two fibrils differ in fundamental properties, such as presence of right-hand or left-hand twisted cross-beta sheets and overall fold of the fibril proteins. Yet, both proteins adopt highly similar beta-arch conformations within the N-terminal similar to 21 residues. Our data demonstrate the importance of the fibril protein N-terminus for the stability of the analyzed amyloid fibril morphologies and suggest strategies of combating this disease by interfering with specific fibril polymorphs.