Journal
ELIFE
Volume 7, Issue -, Pages -Publisher
ELIFE SCIENCES PUBLICATIONS LTD
DOI: 10.7554/eLife.36402
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Funding
- Schweizerischer Nationalfonds zur Forderung der Wissenschaftlichen Forschung [CRSII3_154461, CRSII5_177195]
- Stiftung Synapsis - Alzheimer Forschung Schweiz AFS Henning Stahlberg
- Swiss National Science Foundation (SNF) [CRSII3_154461] Funding Source: Swiss National Science Foundation (SNF)
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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 angstrom. Two protofilaments form a polar fibril composed of staggered beta-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.
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