气候变化领域集成服务门户(CCPortal): Identification and nanomechanical characterization of the fundamental single-strand protofilaments of amyloid α-synuclein fibrils

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DOI	10.1073/pnas.1721220115
	Identification and nanomechanical characterization of the fundamental single-strand protofilaments of amyloid α-synuclein fibrils
	Ruggeri F.S.; Benedetti F.; Knowles T.P.J.; Lashuel H.A.; Sekatskii S.; Dietler G.
发表日期	2018
ISSN	0027-8424
起始页码	7230
结束页码	7235
卷号	115 期号:28
英文摘要	The formation and spreading of amyloid aggregates from the presynaptic protein α-synuclein in the brain play central roles in the pathogenesis of Parkinson’s disease. Here, we use high-resolution atomic force microscopy to investigate the early oligomerization events of α-synuclein with single monomer angstrom resolution. We identify, visualize, and characterize directly the smallest elementary unit in the hierarchical assembly of amyloid fibrils, termed here single-strand protofilaments. We show that protofilaments form from the direct molecular assembly of unfolded monomeric α-synuclein polypeptide chains. To unravel protofilaments’ internal structure and elastic properties, we manipulated nano-mechanically these species by atomic force spectroscopy. The single-molecule scale identification and characterization of the fundamental unit of amyloid assemblies provide insights into early events underlying their formation and shed light on opportunities for therapeutic intervention at the early stages of aberrant protein self-assembly. © 2018 National Academy of Sciences. All rights reserved.
英文关键词	Amyloid; Atomic force microscopy; Early molecular assembly; Force spectroscopy; Protein aggregation
语种	英语
scopus关键词	alpha synuclein; alpha synuclein; amyloid; SNCA protein, human; Article; atomic force microscopy; biophysics; controlled study; molecular mechanics; nonhuman; oligomerization; priority journal; protein analysis; protein assembly; protein function; protein unfolding; chemistry; human; metabolism; Parkinson disease; pathology; protein unfolding; proteinosis; ultrastructure; alpha-Synuclein; Amyloid; Humans; Microscopy, Atomic Force; Parkinson Disease; Protein Aggregation, Pathological; Protein Unfolding
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/160497
作者单位	Ruggeri, F.S., Laboratory of Physics of Living Matter, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, 1015, Switzerland, Department of Chemistry, University of Cambridge, Cambridge, CB2 1EW, United Kingdom; Benedetti, F., Centre for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, Lausanne, 1015, Switzerland; Knowles, T.P.J., Department of Chemistry, University of Cambridge, Cambridge, CB2 1EW, United Kingdom, Cavendish Laboratory, Department of Physics, University of Cambridge, Cambridge, CB3 0HE, United Kingdom; Lashuel, H.A., Laboratory of Molecular and Chemical Biology of Neurodegeneration, Brain Mind Institute, Faculty of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, 1015, Switzerland; Sekatskii, S., Laboratory of Physics of Living Matter, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, 1015, Switzerland; Dietler, G., Laboratory of Physics of Living Matter, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, 1015,...
推荐引用方式 GB/T 7714	Ruggeri F.S.,Benedetti F.,Knowles T.P.J.,et al. Identification and nanomechanical characterization of the fundamental single-strand protofilaments of amyloid α-synuclein fibrils[J],2018,115(28).
APA	Ruggeri F.S.,Benedetti F.,Knowles T.P.J.,Lashuel H.A.,Sekatskii S.,&Dietler G..(2018).Identification and nanomechanical characterization of the fundamental single-strand protofilaments of amyloid α-synuclein fibrils.Proceedings of the National Academy of Sciences of the United States of America,115(28).
MLA	Ruggeri F.S.,et al."Identification and nanomechanical characterization of the fundamental single-strand protofilaments of amyloid α-synuclein fibrils".Proceedings of the National Academy of Sciences of the United States of America 115.28(2018).