Structural Basis for Dityrosine-Mediated Inhibition of alpha-Synuclein Fibrillization

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

Standard

Structural Basis for Dityrosine-Mediated Inhibition of alpha-Synuclein Fibrillization. / Sahin, Cagla; Osterlund, Eva Christina; Osterlund, Nicklas; Costeira-Paulo, Joana; Pedersen, Jannik Nedergaard; Christiansen, Gunna; Nielsen, Janni; Grønnemose, Anne Louise; Amstrup, Søren Kirk; Tiwari, Manish K.; Rao, R. Shyama Prasad; Bjerrum, Morten Jannik; Ilag, Leopold L.; Davies, Michael J.; Marklund, Erik G.; Pedersen, Jan Skov; Landreh, Michael; Moller, Ian Max; Jorgensen, Thomas J. D.; Otzen, Daniel Erik.

In: Journal of the American Chemical Society, Vol. 144, No. 27, 2022, p. 11949-11954.

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

Harvard

Sahin, C, Osterlund, EC, Osterlund, N, Costeira-Paulo, J, Pedersen, JN, Christiansen, G, Nielsen, J, Grønnemose, AL, Amstrup, SK, Tiwari, MK, Rao, RSP, Bjerrum, MJ, Ilag, LL, Davies, MJ, Marklund, EG, Pedersen, JS, Landreh, M, Moller, IM, Jorgensen, TJD & Otzen, DE 2022, 'Structural Basis for Dityrosine-Mediated Inhibition of alpha-Synuclein Fibrillization', Journal of the American Chemical Society, vol. 144, no. 27, pp. 11949-11954. https://doi.org/10.1021/jacs.2c03607

APA

Sahin, C., Osterlund, E. C., Osterlund, N., Costeira-Paulo, J., Pedersen, J. N., Christiansen, G., Nielsen, J., Grønnemose, A. L., Amstrup, S. K., Tiwari, M. K., Rao, R. S. P., Bjerrum, M. J., Ilag, L. L., Davies, M. J., Marklund, E. G., Pedersen, J. S., Landreh, M., Moller, I. M., Jorgensen, T. J. D., & Otzen, D. E. (2022). Structural Basis for Dityrosine-Mediated Inhibition of alpha-Synuclein Fibrillization. Journal of the American Chemical Society, 144(27), 11949-11954. https://doi.org/10.1021/jacs.2c03607

Vancouver

Sahin C, Osterlund EC, Osterlund N, Costeira-Paulo J, Pedersen JN, Christiansen G et al. Structural Basis for Dityrosine-Mediated Inhibition of alpha-Synuclein Fibrillization. Journal of the American Chemical Society. 2022;144(27):11949-11954. https://doi.org/10.1021/jacs.2c03607

Author

Sahin, Cagla ; Osterlund, Eva Christina ; Osterlund, Nicklas ; Costeira-Paulo, Joana ; Pedersen, Jannik Nedergaard ; Christiansen, Gunna ; Nielsen, Janni ; Grønnemose, Anne Louise ; Amstrup, Søren Kirk ; Tiwari, Manish K. ; Rao, R. Shyama Prasad ; Bjerrum, Morten Jannik ; Ilag, Leopold L. ; Davies, Michael J. ; Marklund, Erik G. ; Pedersen, Jan Skov ; Landreh, Michael ; Moller, Ian Max ; Jorgensen, Thomas J. D. ; Otzen, Daniel Erik. / Structural Basis for Dityrosine-Mediated Inhibition of alpha-Synuclein Fibrillization. In: Journal of the American Chemical Society. 2022 ; Vol. 144, No. 27. pp. 11949-11954.

Bibtex

@article{8aaeb14e13b24eeb89c962c2b4410761,
title = "Structural Basis for Dityrosine-Mediated Inhibition of alpha-Synuclein Fibrillization",
abstract = "alpha-Synuclein (alpha-Syn) is an intrinsically disordered protein which self-assembles into highly organized beta-sheet structures that accumulate in plaques in brains of Parkinson's disease patients. Oxidative stress influences alpha-Syn structure and selfassembly; however, the basis for this remains unclear. Here we characterize the chemical and physical effects of mild oxidation on monomeric alpha-Syn and its aggregation. Using a combination of biophysical methods, small-angle X-ray scattering, and native ion mobility mass spectrometry, we find that oxidation leads to formation of intramolecular dityrosine cross-linkages and a compaction of the alpha-Syn monomer by a factor of root 2. Oxidation-induced compaction is shown to inhibit ordered self-assembly and amyloid formation by steric hindrance, suggesting an important role of mild oxidation in preventing amyloid formation.",
keywords = "METAL-CATALYZED OXIDATION, FIBRILLATION, COPPER(II), OLIGOMERS, BINDING",
author = "Cagla Sahin and Osterlund, {Eva Christina} and Nicklas Osterlund and Joana Costeira-Paulo and Pedersen, {Jannik Nedergaard} and Gunna Christiansen and Janni Nielsen and Gr{\o}nnemose, {Anne Louise} and Amstrup, {S{\o}ren Kirk} and Tiwari, {Manish K.} and Rao, {R. Shyama Prasad} and Bjerrum, {Morten Jannik} and Ilag, {Leopold L.} and Davies, {Michael J.} and Marklund, {Erik G.} and Pedersen, {Jan Skov} and Michael Landreh and Moller, {Ian Max} and Jorgensen, {Thomas J. D.} and Otzen, {Daniel Erik}",
year = "2022",
doi = "10.1021/jacs.2c03607",
language = "English",
volume = "144",
pages = "11949--11954",
journal = "Journal of the American Chemical Society",
issn = "0002-7863",
publisher = "ACS Publications",
number = "27",

}

RIS

TY - JOUR

T1 - Structural Basis for Dityrosine-Mediated Inhibition of alpha-Synuclein Fibrillization

AU - Sahin, Cagla

AU - Osterlund, Eva Christina

AU - Osterlund, Nicklas

AU - Costeira-Paulo, Joana

AU - Pedersen, Jannik Nedergaard

AU - Christiansen, Gunna

AU - Nielsen, Janni

AU - Grønnemose, Anne Louise

AU - Amstrup, Søren Kirk

AU - Tiwari, Manish K.

AU - Rao, R. Shyama Prasad

AU - Bjerrum, Morten Jannik

AU - Ilag, Leopold L.

AU - Davies, Michael J.

AU - Marklund, Erik G.

AU - Pedersen, Jan Skov

AU - Landreh, Michael

AU - Moller, Ian Max

AU - Jorgensen, Thomas J. D.

AU - Otzen, Daniel Erik

PY - 2022

Y1 - 2022

N2 - alpha-Synuclein (alpha-Syn) is an intrinsically disordered protein which self-assembles into highly organized beta-sheet structures that accumulate in plaques in brains of Parkinson's disease patients. Oxidative stress influences alpha-Syn structure and selfassembly; however, the basis for this remains unclear. Here we characterize the chemical and physical effects of mild oxidation on monomeric alpha-Syn and its aggregation. Using a combination of biophysical methods, small-angle X-ray scattering, and native ion mobility mass spectrometry, we find that oxidation leads to formation of intramolecular dityrosine cross-linkages and a compaction of the alpha-Syn monomer by a factor of root 2. Oxidation-induced compaction is shown to inhibit ordered self-assembly and amyloid formation by steric hindrance, suggesting an important role of mild oxidation in preventing amyloid formation.

AB - alpha-Synuclein (alpha-Syn) is an intrinsically disordered protein which self-assembles into highly organized beta-sheet structures that accumulate in plaques in brains of Parkinson's disease patients. Oxidative stress influences alpha-Syn structure and selfassembly; however, the basis for this remains unclear. Here we characterize the chemical and physical effects of mild oxidation on monomeric alpha-Syn and its aggregation. Using a combination of biophysical methods, small-angle X-ray scattering, and native ion mobility mass spectrometry, we find that oxidation leads to formation of intramolecular dityrosine cross-linkages and a compaction of the alpha-Syn monomer by a factor of root 2. Oxidation-induced compaction is shown to inhibit ordered self-assembly and amyloid formation by steric hindrance, suggesting an important role of mild oxidation in preventing amyloid formation.

KW - METAL-CATALYZED OXIDATION

KW - FIBRILLATION

KW - COPPER(II)

KW - OLIGOMERS

KW - BINDING

U2 - 10.1021/jacs.2c03607

DO - 10.1021/jacs.2c03607

M3 - Journal article

C2 - 35749730

VL - 144

SP - 11949

EP - 11954

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

SN - 0002-7863

IS - 27

ER -

ID: 313053298