N-Terminal Acetylation of alpha-Synuclein Slows down Its Aggregation Process and Alters the Morphology of the Resulting Aggregates

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

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N-Terminal Acetylation of alpha-Synuclein Slows down Its Aggregation Process and Alters the Morphology of the Resulting Aggregates. / Bell, Rosie; Thrush, Rebecca J.; Castellana-Cruz, Marta; Oeller, Marc; Staats, Roxine; Nene, Aishwarya; Flagmeier, Patrick; Xu, Catherine K.; Satapathy, Sandeep; Galvagnion, Celine; Wilson, Mark R.; Dobson, Christopher M.; Kumita, Janet R.; Vendruscolo, Michele.

In: Biochemistry, Vol. 61, No. 17, 2022, p. 1743–1756.

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

Harvard

Bell, R, Thrush, RJ, Castellana-Cruz, M, Oeller, M, Staats, R, Nene, A, Flagmeier, P, Xu, CK, Satapathy, S, Galvagnion, C, Wilson, MR, Dobson, CM, Kumita, JR & Vendruscolo, M 2022, 'N-Terminal Acetylation of alpha-Synuclein Slows down Its Aggregation Process and Alters the Morphology of the Resulting Aggregates', Biochemistry, vol. 61, no. 17, pp. 1743–1756. https://doi.org/10.1021/acs.biochem.2c00104

APA

Bell, R., Thrush, R. J., Castellana-Cruz, M., Oeller, M., Staats, R., Nene, A., Flagmeier, P., Xu, C. K., Satapathy, S., Galvagnion, C., Wilson, M. R., Dobson, C. M., Kumita, J. R., & Vendruscolo, M. (2022). N-Terminal Acetylation of alpha-Synuclein Slows down Its Aggregation Process and Alters the Morphology of the Resulting Aggregates. Biochemistry, 61(17), 1743–1756. https://doi.org/10.1021/acs.biochem.2c00104

Vancouver

Bell R, Thrush RJ, Castellana-Cruz M, Oeller M, Staats R, Nene A et al. N-Terminal Acetylation of alpha-Synuclein Slows down Its Aggregation Process and Alters the Morphology of the Resulting Aggregates. Biochemistry. 2022;61(17):1743–1756. https://doi.org/10.1021/acs.biochem.2c00104

Author

Bell, Rosie ; Thrush, Rebecca J. ; Castellana-Cruz, Marta ; Oeller, Marc ; Staats, Roxine ; Nene, Aishwarya ; Flagmeier, Patrick ; Xu, Catherine K. ; Satapathy, Sandeep ; Galvagnion, Celine ; Wilson, Mark R. ; Dobson, Christopher M. ; Kumita, Janet R. ; Vendruscolo, Michele. / N-Terminal Acetylation of alpha-Synuclein Slows down Its Aggregation Process and Alters the Morphology of the Resulting Aggregates. In: Biochemistry. 2022 ; Vol. 61, No. 17. pp. 1743–1756.

Bibtex

@article{d8afc4e7816b47ca83a7cd913f52cae6,
title = "N-Terminal Acetylation of alpha-Synuclein Slows down Its Aggregation Process and Alters the Morphology of the Resulting Aggregates",
abstract = "Parkinson's disease is associated with the aberrant aggregation of alpha-synuclein. Although the causes of this process are still unclear, post-translational modifications of alpha-synuclein are likely to play a modulatory role. Since alpha-synuclein is constitutively N-terminally acetylated, we investigated how this post-translational modification alters the aggregation behavior of this protein. By applying a three-pronged aggregation kinetics approach, we observed that N-terminal acetylation results in a reduced rate of lipid-induced aggregation and slows down both elongation and fibrilcatalyzed aggregate proliferation. An analysis of the amyloid fibrils produced by the aggregation process revealed different morphologies for the acetylated and nonacetylated forms in both lipid-induced aggregation and seed-induced aggregation assays. In addition, we found that fibrils formed by acetylated alpha-synuclein exhibit a lower beta-sheet content. These findings indicate that N-terminal acetylation of alpha-synuclein alters its lipid-dependent aggregation behavior, reduces its rate of in vitro aggregation, and affects the structural properties of its fibrillar aggregates.",
keywords = "DISEASE, MUTATION, PARKINSON, TOXICITY, GENETICS, BINDING, IMPACT",
author = "Rosie Bell and Thrush, {Rebecca J.} and Marta Castellana-Cruz and Marc Oeller and Roxine Staats and Aishwarya Nene and Patrick Flagmeier and Xu, {Catherine K.} and Sandeep Satapathy and Celine Galvagnion and Wilson, {Mark R.} and Dobson, {Christopher M.} and Kumita, {Janet R.} and Michele Vendruscolo",
year = "2022",
doi = "10.1021/acs.biochem.2c00104",
language = "English",
volume = "61",
pages = "1743–1756",
journal = "Biochemistry",
issn = "0006-2960",
publisher = "American Chemical Society",
number = "17",

}

RIS

TY - JOUR

T1 - N-Terminal Acetylation of alpha-Synuclein Slows down Its Aggregation Process and Alters the Morphology of the Resulting Aggregates

AU - Bell, Rosie

AU - Thrush, Rebecca J.

AU - Castellana-Cruz, Marta

AU - Oeller, Marc

AU - Staats, Roxine

AU - Nene, Aishwarya

AU - Flagmeier, Patrick

AU - Xu, Catherine K.

AU - Satapathy, Sandeep

AU - Galvagnion, Celine

AU - Wilson, Mark R.

AU - Dobson, Christopher M.

AU - Kumita, Janet R.

AU - Vendruscolo, Michele

PY - 2022

Y1 - 2022

N2 - Parkinson's disease is associated with the aberrant aggregation of alpha-synuclein. Although the causes of this process are still unclear, post-translational modifications of alpha-synuclein are likely to play a modulatory role. Since alpha-synuclein is constitutively N-terminally acetylated, we investigated how this post-translational modification alters the aggregation behavior of this protein. By applying a three-pronged aggregation kinetics approach, we observed that N-terminal acetylation results in a reduced rate of lipid-induced aggregation and slows down both elongation and fibrilcatalyzed aggregate proliferation. An analysis of the amyloid fibrils produced by the aggregation process revealed different morphologies for the acetylated and nonacetylated forms in both lipid-induced aggregation and seed-induced aggregation assays. In addition, we found that fibrils formed by acetylated alpha-synuclein exhibit a lower beta-sheet content. These findings indicate that N-terminal acetylation of alpha-synuclein alters its lipid-dependent aggregation behavior, reduces its rate of in vitro aggregation, and affects the structural properties of its fibrillar aggregates.

AB - Parkinson's disease is associated with the aberrant aggregation of alpha-synuclein. Although the causes of this process are still unclear, post-translational modifications of alpha-synuclein are likely to play a modulatory role. Since alpha-synuclein is constitutively N-terminally acetylated, we investigated how this post-translational modification alters the aggregation behavior of this protein. By applying a three-pronged aggregation kinetics approach, we observed that N-terminal acetylation results in a reduced rate of lipid-induced aggregation and slows down both elongation and fibrilcatalyzed aggregate proliferation. An analysis of the amyloid fibrils produced by the aggregation process revealed different morphologies for the acetylated and nonacetylated forms in both lipid-induced aggregation and seed-induced aggregation assays. In addition, we found that fibrils formed by acetylated alpha-synuclein exhibit a lower beta-sheet content. These findings indicate that N-terminal acetylation of alpha-synuclein alters its lipid-dependent aggregation behavior, reduces its rate of in vitro aggregation, and affects the structural properties of its fibrillar aggregates.

KW - DISEASE

KW - MUTATION

KW - PARKINSON

KW - TOXICITY

KW - GENETICS

KW - BINDING

KW - IMPACT

U2 - 10.1021/acs.biochem.2c00104

DO - 10.1021/acs.biochem.2c00104

M3 - Journal article

C2 - 35944093

VL - 61

SP - 1743

EP - 1756

JO - Biochemistry

JF - Biochemistry

SN - 0006-2960

IS - 17

ER -

ID: 318528026