β-Synuclein suppresses both the initiation and amplification steps of α-synuclein aggregation via competitive binding to surfaces
Research output: Contribution to journal › Journal article › Research › peer-review
α-Synuclein is an intrinsically disordered protein that is associated with the pathogenesis of Parkinson's disease through the processes involved in the formation of amyloid fibrils. α and β-synuclein are homologous proteins found at comparable levels in presynaptic terminals but β-synuclein has a greatly reduced propensity to aggregate and indeed has been found to inhibit α-synuclein aggregation. In this paper, we describe how sequence differences between α- and β-synuclein affect individual microscopic processes in amyloid formation. In particular, we show that β-synuclein strongly suppresses both lipid-induced aggregation and secondary nucleation of α-synuclein by competing for binding sites at the surfaces of lipid vesicles and fibrils, respectively. These results suggest that β-synuclein can act as a natural inhibitor of α-synuclein aggregation by reducing both the initiation of its self-assembly and the proliferation of its aggregates.
Original language | English |
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Journal | Scientific Reports |
Volume | 6 |
Pages (from-to) | 36010 |
ISSN | 2045-2322 |
DOIs | |
Publication status | Published - 3 Nov 2016 |
Externally published | Yes |
- Amino Acid Sequence, Binding, Competitive, Hydrogen-Ion Concentration, Lipids/chemistry, Phosphatidylserines/chemistry, Protein Aggregates, Protein Aggregation, Pathological, Protein Binding, Sequence Alignment, Surface Properties, alpha-Synuclein/chemistry, beta-Synuclein/chemistry
Research areas
ID: 216263682