Yuan Yu, Dong Xiaozhe, Wang Huan, Gai Feng
Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
Biophys Rev (Melville). 2024 Aug 13;5(3):032104. doi: 10.1063/5.0222349. eCollection 2024 Sep.
Protein/peptide amyloid fibril formation is associated with various neurodegenerative diseases and, hence, has been the subject of extensive studies. From a structure-evolution point of view, we now know a great deal about the initial and final states of this process; however, we know very little about its intermediate states. Herein, we employ liquid-phase transmission electron microscopy to directly visualize the formation of one of the intermediates formed during the aggregation process of an amyloid-forming peptide. As shown in figure, we find that Aβ42, the amyloid formation of which has been linked to the development of Alzheimer's disease, can populate a ring-shaped intermediate structure with a diameter of tens of nanometers; additionally, the air-liquid interface can "catalyze" the formation of amyloid fibrils.
蛋白质/肽类淀粉样纤维的形成与多种神经退行性疾病相关，因此一直是广泛研究的主题。从结构演化的角度来看，我们现在对这个过程的初始和最终状态了解很多；然而，我们对其中间状态却知之甚少。在此，我们利用液相透射电子显微镜直接观察淀粉样形成肽聚集过程中形成的一种中间体的形成情况。如图所示，我们发现与阿尔茨海默病发展相关的Aβ42能够形成直径为几十纳米的环形中间结构；此外，气液界面可以“催化”淀粉样纤维的形成。
