Institute of Biological Information Processing, Structural Biochemistry (IBI-7) and JuStruct, Jülich Center for Structural Biology, Forschungszentrum Jülich, Jülich, Germany.
Institute of Biological Information Processing, Structural Biochemistry (IBI-7) and JuStruct, Jülich Center for Structural Biology, Forschungszentrum Jülich, Jülich, Germany; Institut für Physikalische Biologie, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany.
J Biol Chem. 2021 Aug;297(2):100938. doi: 10.1016/j.jbc.2021.100938. Epub 2021 Jul 3.
Amyloids share a common architecture but play disparate biological roles in processes ranging from bacterial defense mechanisms to protein misfolding diseases. Their structures are highly polymorphic, which makes them difficult to study by X-ray diffraction or NMR spectroscopy. Our understanding of amyloid structures is due in large part to recent advances in the field of cryo-EM, which allows for determining the polymorphs separately. In this review, we highlight the main stepping stones leading to the substantial number of high-resolution amyloid fibril structures known today as well as recent developments regarding automation and software in cryo-EM. We discuss that sample preparation should move closer to physiological conditions to understand how amyloid aggregation and disease are linked. We further highlight new approaches to address heterogeneity and polymorphism of amyloid fibrils in EM image processing and give an outlook to the upcoming challenges in researching the structural biology of amyloids.
淀粉样纤维共享一种共同的结构，但在从细菌防御机制到蛋白质错误折叠疾病等各种过程中发挥不同的生物学作用。它们的结构高度多态性，这使得通过 X 射线衍射或 NMR 光谱学来研究它们变得非常困难。我们对淀粉样纤维结构的理解在很大程度上要归功于冷冻电镜领域的最新进展，该技术可以分别确定多晶型物。在这篇综述中，我们重点介绍了导致当今大量高分辨率淀粉样纤维结构的主要里程碑，以及冷冻电镜中自动化和软件方面的最新进展。我们讨论了应该使样品制备更接近生理条件，以了解淀粉样聚集和疾病之间的联系。我们进一步强调了在 EM 图像处理中解决淀粉样纤维异质性和多态性的新方法，并展望了研究淀粉样纤维结构生物学的未来挑战。
