The fold of α-synuclein fibrils

Vilar, Marçal ; Chou, Hui-Ting ; Lührs, Thorsten ; Maji, Samir K. ; Riek-Loher, Dominique ; Verel, Rene ; Manning, Gerard ; Stahlberg, Henning ; Riek, Roland (2008) The fold of α-synuclein fibrils Proceedings of the National Academy of Sciences, 105 (25). pp. 8637-8642. ISSN 0027-8424

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Official URL: http://doi.org/10.1073/pnas.0712179105

Related URL: http://dx.doi.org/10.1073/pnas.0712179105

Abstract

The aggregation of proteins into amyloid fibrils is associated with several neurodegenerative diseases. In Parkinson's disease it is believed that the aggregation of α-synuclein (α-syn) from monomers by intermediates into amyloid fibrils is the toxic disease-causative mechanism. Here, we studied the structure of α-syn in its amyloid state by using various biophysical approaches. Quenched hydrogen/deuterium exchange NMR spectroscopy identified five β-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 β-sheet secondary structure. The data suggest that β1-strand interacts with β2, β2 with β3, β3 with β4, and β4 with β5. High-resolution cryoelectron microscopy revealed the protofilament boundaries of ≈2 × 3.5 nm. Based on the combination of these data and published structural studies, a fold of α-syn in the fibrils is proposed and discussed. • amyloid • NMR • Parkinson's disease • structure • aggregation

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Deposited On:14 Nov 2022 04:06
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