Identification and nanomechanical characterization of the fundamental single-strand protofilaments of amyloid α-synuclein fibrils.

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State: Serval
Version: Final published version
Serval ID
serval:BIB_A49EC9CE5710
Type
Article: article from journal or magazin.
Collection
Publications
Title
Identification and nanomechanical characterization of the fundamental single-strand protofilaments of amyloid α-synuclein fibrils.
Journal
Proceedings of the National Academy of Sciences of the United States of America
Author(s)
Ruggeri F.S., Benedetti F., Knowles TPJ, Lashuel H.A., Sekatskii S., Dietler G.
ISSN
1091-6490 (Electronic)
ISSN-L
0027-8424
Publication state
Published
Issued date
2018
Peer-reviewed
Oui
Volume
115
Number
28
Pages
7230-7235
Language
english
Abstract
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 nanomechanically 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.
Keywords
amyloid, atomic force microscopy, early molecular assembly, force spectroscopy, protein aggregation
Pubmed
Web of science
Open Access
Yes
Create date
29/06/2018 17:29
Last modification date
08/05/2019 23:10
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