气候变化领域集成服务门户(CCPortal): Structural insights into α-synuclein monomer

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DOI	10.1073/pnas.2012171118
	Structural insights into α-synuclein monomer–fibril interactions
	Kumari P.; Ghosh D.; Vanas A.; Fleischmann Y.; Wiegand T.; Jeschke G.; Riek R.; Eichmann C.
发表日期	2021
ISSN	00278424
卷号	118 期号:10
英文摘要	Protein aggregation into amyloid fibrils is associated with multiple neurodegenerative diseases, including Parkinson’s disease. Kinetic data and biophysical characterization have shown that the secondary nucleation pathway highly accelerates aggregation via the absorption of monomeric protein on the surface of amyloid fibrils. Here, we used NMR and electron paramagnetic resonance spectroscopy to investigate the interaction of monomeric α-synuclein (α-Syn) with its fibrillar form. We demonstrate that α-Syn monomers interact transiently via their positively charged N terminus with the negatively charged flexible C-terminal ends of the fibrils. These intermolecular interactions reduce intramolecular contacts in monomeric α-Syn, yielding further unfolding of the partially collapsed intrinsically disordered states of α-Syn along with a possible increase in the local concentration of soluble α-Syn and alignment of individual monomers on the fibril surface. Our data indicate that intramolecular unfolding critically contributes to the aggregation kinetics of α-Syn during secondary nucleation. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Parkinson’s disease; Protein aggregation; Secondary nucleation; α-synuclein
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180373
作者单位	Department of Chemistry and Applied Biosciences, Laboratory of Physical Chemistry, ETH Zurich, Zurich, 8093, Switzerland; Department of Biological Regulation, Weizmann Institute of Science, Rehovot, 76100, Israel
推荐引用方式 GB/T 7714	Kumari P.,Ghosh D.,Vanas A.,等. Structural insights into α-synuclein monomer–fibril interactions[J],2021,118(10).
APA	Kumari P..,Ghosh D..,Vanas A..,Fleischmann Y..,Wiegand T..,...&Eichmann C..(2021).Structural insights into α-synuclein monomer–fibril interactions.Proceedings of the National Academy of Sciences of the United States of America,118(10).
MLA	Kumari P.,et al."Structural insights into α-synuclein monomer–fibril interactions".Proceedings of the National Academy of Sciences of the United States of America 118.10(2021).