Cryo-EM of amyloid fibrils and cellular aggregates
Cryo-EM of amyloid fibrils and cellular aggregates
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DOI：
10.1016/j.sbi.2019.05.003
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发表时间：
2019-10-01
影响因子：
6.8
通讯作者：
Saibil, Helen R.
中科院分区：
文献类型：
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作者：
Fitzpatrick, Anthony W. P.;Saibil, Helen R.
神经退行性疾病和其他蛋白质错误折叠疾病与蛋白质聚集有关，蛋白质可能在疾病的遗传形式中发生突变，或者在晚发散发性疾病中发生野生型形式突变。可能涉及多种蛋白质和肽，其聚集源自天然折叠或天然非结构化物种。淀粉样原纤维的大量沉积通常与晚期病理学中的细胞死亡有关。在这篇综述中，我们阐述了冷冻电镜和相关方法对从患者大脑中提取或体外形成的淀粉样原纤维结构测定的贡献。我们还讨论了蛋白质聚集的细胞模型以及电子断层扫描对理解聚集的细胞背景的贡献。
Neurodegenerative and other protein misfolding diseases are associated with the aggregation of a protein, which may be mutated in genetic forms of disease, or the wild type form in late onset sporadic disease. A wide variety of proteins and peptides can be involved, with aggregation originating from a natively folded or a natively unstructured species. Large deposits of amyloid fibrils are typically associated with cell death in late stage pathology. In this review, we illustrate the contributions of cryo-EM and related methods to the structure determination of amyloid fibrils extracted post mortem from patient brains or formed in vitro. We also discuss cell models of protein aggregation and the contributions of electron tomography to understanding the cellular context of aggregation.