Department of Biology, Technion-Israel Institute of Technology, Haifa 3200003, Israel.
Department of Biology, Technion-Israel Institute of Technology, Haifa 3200003, Israel; European Molecular Biology Laboratory (EMBL), Hamburg 22607, Germany.
Curr Opin Struct Biol. 2021 Jun;68:184-193. doi: 10.1016/j.sbi.2021.01.006. Epub 2021 Feb 22.
The amyloid state of protein aggregation is associated with neurodegenerative and systemic diseases but can play physiological roles in many organisms, including as stress granules and virulence determinants. The recent resolution revolution in cryogenic electron microscopy (cryo-EM) has significantly expanded the repertoire of high-resolution amyloid structures, to include, for the first-time, fibrils extracted ex vivo in addition to those formed, or seeded, in vitro. Here, we review recently solved cryo-EM amyloid structures, and compare amino acid prevalence, in efforts to systematically distinguish between pathological and functional amyloids, even though such structural classification is hindered by extensive polymorphism even among fibrils of the same protein, and by dual functioning of some human amyloids in both physiological activities and disease mechanisms. Forthcoming structures of bacterial amyloids may expose specific, evolutionary-designed properties specific to functional fibrils.
蛋白质聚集的淀粉样状态与神经退行性和全身性疾病有关，但在许多生物体中发挥生理作用，包括应激颗粒和毒力决定因素。低温电子显微镜（cryo-EM）的最新分辨率革命极大地扩展了高分辨率淀粉样结构的范围，首次包括了除体外形成或接种的纤维以外的体外提取的纤维。在这里，我们回顾了最近解决的 cryo-EM 淀粉样结构，并比较了氨基酸的普遍性，努力系统地区分病理性和功能性淀粉样蛋白，尽管即使在同一蛋白质的纤维之间也存在广泛的多态性，并且一些人类淀粉样蛋白在生理活动和疾病机制中具有双重功能，这种结构分类受到阻碍。即将出现的细菌淀粉样蛋白结构可能会揭示特定的、进化设计的功能性纤维的特性。
