Cryo-EM structure of alpha-synuclein fibrils

Research output: Contribution to journalJournal articlepeer-review

  • Ricardo Guerrero-Ferreira
  • Taylor, Nicholas M I
  • Daniel Mona
  • Philippe Ringler
  • Matthias E Lauer
  • Roland Riek
  • Markus Britschgi
  • Henning Stahlberg

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 languageEnglish
JournaleLife
Volume7
ISSN2050-084X
DOIs
Publication statusPublished - 2018
Externally publishedYes

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