Vilar, MarcalChou, Hui-TingLuehrs, ThorstenMaji, Samir K.Riek-Loher, DominiqueVerel, ReneManning, GerardStahlberg, HenningRiek, Roland2020-02-132020-02-132020-02-132008-06-1210.1073/pnas.0712179105https://infoscience.epfl.ch/handle/20.500.14299/165382The aggregation of proteins into amyloid fibrils is associated with several neurodegenerative diseases. In Parkinson's disease it is believed that the aggregation of a-synuclein (alpha-syn) from monomers by intermediates into amyloid fibrils is the toxic disease-causative mechanism. Here, we studied the structure of a-syn in its amyloid state by using various biophysical approaches. Quenched hydrogen/deuterium exchange NMR spectroscopy identified five beta-strands within the fibril core comprising residues 35-96 and solid-state NMR data from amyloid fibrils comprising the fibril core residues 30-110 confirmed the presence of beta-sheet secondary structure. The data suggest that beta 1-strand interacts with beta 2, beta 2 with beta 3, beta 3 with beta 4, and beta 4 with beta 5. High-resolution cryoelectron microscopy revealed the protofilament boundaries of approximate to 2 x 3.5 nm. Based on the combination of these data and published structural studies, a fold of alpha-syn in the fibrils is proposed and discussed.text::journal::journal article::research article