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

Standard

β-Synuclein suppresses both the initiation and amplification steps of α-synuclein aggregation via competitive binding to surfaces. / Brown, James W P; Buell, Alexander K; Michaels, Thomas C T; Meisl, Georg; Carozza, Jacqueline; Flagmeier, Patrick; Vendruscolo, Michele; Knowles, Tuomas P J; Dobson, Christopher M; Galvagnion, Céline.

In: Scientific Reports, Vol. 6, 03.11.2016, p. 36010.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Brown, JWP, Buell, AK, Michaels, TCT, Meisl, G, Carozza, J, Flagmeier, P, Vendruscolo, M, Knowles, TPJ, Dobson, CM & Galvagnion, C 2016, 'β-Synuclein suppresses both the initiation and amplification steps of α-synuclein aggregation via competitive binding to surfaces', Scientific Reports, vol. 6, pp. 36010. https://doi.org/10.1038/srep36010

APA

Brown, J. W. P., Buell, A. K., Michaels, T. C. T., Meisl, G., Carozza, J., Flagmeier, P., Vendruscolo, M., Knowles, T. P. J., Dobson, C. M., & Galvagnion, C. (2016). β-Synuclein suppresses both the initiation and amplification steps of α-synuclein aggregation via competitive binding to surfaces. Scientific Reports, 6, 36010. https://doi.org/10.1038/srep36010

Vancouver

Brown JWP, Buell AK, Michaels TCT, Meisl G, Carozza J, Flagmeier P et al. β-Synuclein suppresses both the initiation and amplification steps of α-synuclein aggregation via competitive binding to surfaces. Scientific Reports. 2016 Nov 3;6:36010. https://doi.org/10.1038/srep36010

Author

Brown, James W P ; Buell, Alexander K ; Michaels, Thomas C T ; Meisl, Georg ; Carozza, Jacqueline ; Flagmeier, Patrick ; Vendruscolo, Michele ; Knowles, Tuomas P J ; Dobson, Christopher M ; Galvagnion, Céline. / β-Synuclein suppresses both the initiation and amplification steps of α-synuclein aggregation via competitive binding to surfaces. In: Scientific Reports. 2016 ; Vol. 6. pp. 36010.

Bibtex

@article{695825bd1a434329a3e27a6ab296b4f4,
title = "β-Synuclein suppresses both the initiation and amplification steps of α-synuclein aggregation via competitive binding to surfaces",
abstract = "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.",
keywords = "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",
author = "Brown, {James W P} and Buell, {Alexander K} and Michaels, {Thomas C T} and Georg Meisl and Jacqueline Carozza and Patrick Flagmeier and Michele Vendruscolo and Knowles, {Tuomas P J} and Dobson, {Christopher M} and C{\'e}line Galvagnion",
year = "2016",
month = nov,
day = "3",
doi = "10.1038/srep36010",
language = "English",
volume = "6",
pages = "36010",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - β-Synuclein suppresses both the initiation and amplification steps of α-synuclein aggregation via competitive binding to surfaces

AU - Brown, James W P

AU - Buell, Alexander K

AU - Michaels, Thomas C T

AU - Meisl, Georg

AU - Carozza, Jacqueline

AU - Flagmeier, Patrick

AU - Vendruscolo, Michele

AU - Knowles, Tuomas P J

AU - Dobson, Christopher M

AU - Galvagnion, Céline

PY - 2016/11/3

Y1 - 2016/11/3

N2 - 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.

AB - 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.

KW - Amino Acid Sequence

KW - Binding, Competitive

KW - Hydrogen-Ion Concentration

KW - Lipids/chemistry

KW - Phosphatidylserines/chemistry

KW - Protein Aggregates

KW - Protein Aggregation, Pathological

KW - Protein Binding

KW - Sequence Alignment

KW - Surface Properties

KW - alpha-Synuclein/chemistry

KW - beta-Synuclein/chemistry

U2 - 10.1038/srep36010

DO - 10.1038/srep36010

M3 - Journal article

C2 - 27808107

VL - 6

SP - 36010

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

ER -

ID: 216263682