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bioRxiv · 10.1101/276436

Cryo-EM structure of alpha-synuclein fibrils

Guerrero-Ferreira, R.·Taylor, N. M. I.·Mona, D.·Ringler, P.·Lauer, M. E.·Riek, R.·Britschgi, M.·Stahlberg, H.
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Abstract

Intracellular inclusions of alpha-synuclein are the neuropathological hallmark of progressive disorders called synucleinopathies. Alpha-synuclein fibrils are associated with transmissive cell-to-cell propagation of pathology. We report the structure of an alpha-synuclein fibril (residues 1-121) determined by cryo-electron microscopy at 3.4[A] resolution. 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 mutation sites associated with familial synucleinopathies, form the interface between the two protofilaments and contribute to fibril stability. A hydrophobic cleft may have implications for fibril elongation, and inform the rational design of molecules for diagnosis and treatment of synucleinopathies.

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Guerrero-Ferreira, R., Taylor, N. M. I., Mona, D., Ringler, P., Lauer, M. E., Riek, R., Britschgi, M., Stahlberg, H.. 2018-03-05. Cryo-EM structure of alpha-synuclein fibrils. https://doi.org/10.1101/276436

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