Karina Abramov-Harpaz , Sapir Lan-Mark , Yifat Miller
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引用次数: 0
Abstract
Parkinson's disease (PD) is one of many neurodegenerative diseases. The protein associated with PD is α-synuclein (AS). Aggregation of AS protein into oligomers, protofilaments, and finally to fibrils yields to the development of PD. The aggregation process of AS leads to the formation of polymorphic AS fibrils. Herein, we compared four polymorphic full-length AS1–140 fibrils, using extensive computational tools. The main conclusion of this study emphasizes the role of the structurally packed non-amyloid component (NAC) core domain in AS fibrils. Polymorphic AS fibrils that presented a packed NAC core domain, exhibited more β-sheets and fewer fluctuations in the NAC domain. Hence, these AS fibrils are more stable and populated than the AS fibrils, by which the NAC domains are more exposed, more fluctuate and less packed in the fibrillary structure. Therefore, this study emphasizes the importance of the NAC domain packing in the morphology of AS fibrils. The results obtained in this study will initiate future studies to develop compounds to prevent and inhibit AS aggregation.
帕金森病(PD)是多种神经退行性疾病之一。与帕金森病相关的蛋白质是α-突触核蛋白(AS)。α-突触核蛋白聚集成寡聚体、原丝,最后形成纤维,导致帕金森病的发生。AS的聚集过程会导致多态AS纤维的形成。在此,我们利用大量计算工具比较了四种多态全长 AS1-140 纤维。这项研究的主要结论强调了结构包装的非淀粉样蛋白成分(NAC)核心域在AS纤维中的作用。多态的AS纤维呈挤满的NAC核心域,表现出更多的β片,NAC域的波动较小。因此,这些 AS 纤维比 NAC 结构域在纤维结构中暴露较多、波动较大且排列较少的 AS 纤维更稳定、更多。因此,本研究强调了NAC结构域堆积在AS纤维形态中的重要性。本研究获得的结果将为今后开发预防和抑制 AS 聚合的化合物的研究提供启示。
期刊介绍:
Biophysical Chemistry publishes original work and reviews in the areas of chemistry and physics directly impacting biological phenomena. Quantitative analysis of the properties of biological macromolecules, biologically active molecules, macromolecular assemblies and cell components in terms of kinetics, thermodynamics, spatio-temporal organization, NMR and X-ray structural biology, as well as single-molecule detection represent a major focus of the journal. Theoretical and computational treatments of biomacromolecular systems, macromolecular interactions, regulatory control and systems biology are also of interest to the journal.