
Open access
Author
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Date
2018-07-03Type
- Journal Article
Citations
Cited 286 times in
Web of Science
Cited 306 times in
Scopus
ETH Bibliography
yes
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Abstract
Parkinson’s disease is a progressive neuropathological disorder that belongs to the class of synucleinopathies, in which the protein alpha-synuclein is found at abnormally high concentrations in affected neurons. Its hallmark are intracellular inclusions called Lewy bodies and Lewy neurites. We here report the structure of cytotoxic alpha-synuclein fibrils (residues 1–121), determined by cryo-electron microscopy at a resolution of 3.4 Å. Two protofilaments form a polar fibril composed of staggered β-strands. The backbone of residues 38 to 95, including the fibril core and the non-amyloid component region, are well resolved in the EM map. Residues 50–57, containing three of the mutation sites associated with familial synucleinopathies, form the interface between the two protofilaments and contribute to fibril stability. A hydrophobic cleft at one end of the fibril may have implications for fibril elongation, and invites for the design of molecules for diagnosis and treatment of synucleinopathies. Show more
Permanent link
https://doi.org/10.3929/ethz-b-000284258Publication status
publishedExternal links
Journal / series
eLifeVolume
Pages / Article No.
Publisher
eLife Sciences PublicationsOrganisational unit
03782 - Riek, Roland / Riek, Roland
Funding
154461 - The Time- and Spatially Resolved Aggregation of a-Synuclein and its Relationship to Cell-Cell Transmissibility (SNF)
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Show all metadata
Citations
Cited 286 times in
Web of Science
Cited 306 times in
Scopus
ETH Bibliography
yes
Altmetrics