Cryo-EM structure of alpha-synuclein fibrils
Research output: Contribution to journal › Journal article › peer-review
Parkinson's disease is a progressive neuropathological disorder that belongs to the class of synucleopathies, 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 structure at a resolution of 3.4Å. 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.
Original language | English |
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Journal | eLife |
Volume | 7 |
ISSN | 2050-084X |
DOIs | |
Publication status | Published - 2018 |
Externally published | Yes |
Bibliographical note
Nicholas M.I.Taylor : Present address: Structural Biology of Molecular Machines Group, Protein Structure and Function Programme, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
ID: 199380706