Insights into the molecular mechanism of amyloid filament formation: Segmental folding of α-synuclein on lipid membranes
2021 | journal article; research paper. A publication with affiliation to the University of Göttingen.
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Insights into the molecular mechanism of amyloid filament formation: Segmental folding of α-synuclein on lipid membranes
Antonschmidt, L.; Dervişoğlu, R.; Sant, V.; Tekwani Movellan, K.; Mey, I. P. ; Riedel, D. & Steinem, C. et al. (2021)
Science Advances, 7(20) pp. eabg2174. DOI: https://doi.org/10.1126/sciadv.abg2174
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Details
- Authors
- Antonschmidt, Leif; Dervişoğlu, Rıza; Sant, Vrinda; Tekwani Movellan, Kumar; Mey, Ingo P. ; Riedel, Dietmar ; Steinem, Claudia ; Becker, Stefan T. ; Andreas, Loren B.; Griesinger, Christian
- Abstract
- Recent advances in the structural biology of disease-relevant α-synuclein fibrils have revealed a variety of structures, yet little is known about the process of fibril aggregate formation. Characterization of intermediate species that form during aggregation is crucial; however, this has proven very challenging because of their transient nature, heterogeneity, and low population. Here, we investigate the aggregation of α-synuclein bound to negatively charged phospholipid small unilamellar vesicles. Through a combination of kinetic and structural studies, we identify key time points in the aggregation process that enable targeted isolation of prefibrillar and early fibrillar intermediates. By using solid-state nuclear magnetic resonance, we show the gradual buildup of structural features in an α-synuclein fibril filament, revealing a segmental folding process. We identify distinct membrane-binding domains in α-synuclein aggregates, and the combined data are used to present a comprehensive mechanism of the folding of α-synuclein on lipid membranes.
- Issue Date
- 2021
- Journal
- Science Advances
- Project
- EXC 2067: Multiscale Bioimaging
- Working Group
- RG Griesinger
RG Steinem (Biomolecular Chemistry) - eISSN
- 2375-2548
- Language
- English