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Cryo-EM structure of alpha-synuclein fibrils

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Guerrero-Ferreira Ricardo, Taylor Nicholas MI, Mona Daniel, Ringler Philippe, Lauer Matthias E, Riek Roland, Britschgi Markus, Stahlberg Henning,
Project Molecular and Cellular Modulation in Parkinson's Disease
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Original article (peer-reviewed)

Journal eLife
Volume (Issue) 7
Page(s) e36402
Title of proceedings eLife
DOI 10.7554/elife.36402

Open Access

URL http://doi.org/10.7554/eLife.36402
Type of Open Access Publisher (Gold Open Access)

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.
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