Guerrero-Ferreira, RicardoTaylor, Nicholas M. I.Mona, DanielRingler, PhilippeLauer, Matthias E.Riek, RolandBritschgi, MarkusStahlberg, Henning2020-02-132020-02-132020-02-132018-07-0310.7554/eLife.36402https://infoscience.epfl.ch/handle/20.500.14299/165297Parkinson'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.text::journal::journal article::research article