Structural Basis for Dityrosine-Mediated Inhibition of α-Synuclein Fibrillization
| العنوان: | Structural Basis for Dityrosine-Mediated Inhibition of α-Synuclein Fibrillization |
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| المؤلفون: | Cagla Sahin, Eva Christina Østerlund, Nicklas Österlund, Joana Costeira-Paulo, Jannik Nedergaard Pedersen, Gunna Christiansen, Janni Nielsen, Anne Louise Grønnemose, Søren Kirk Amstrup, Manish K. Tiwari, R. Shyama Prasad Rao, Morten Jannik Bjerrum, Leopold L. Ilag, Michael J. Davies, Erik G. Marklund, Jan Skov Pedersen, Michael Landreh, Ian Max Møller, Thomas J. D. Jørgensen, Daniel Erik Otzen |
| المصدر: | Sahin, C, Østerlund, E C, Österlund, 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, Møller, I M, Jørgensen, T J D & Otzen, D E 2022, ' Structural Basis for Dityrosine-Mediated Inhibition of α-Synuclein Fibrillization ', Journal of the American Chemical Society, vol. 144, no. 27, pp. 11949-11954 . https://doi.org/10.1021/jacs.2c03607 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, vol. 144, no. 27, pp. 11949-11954 . https://doi.org/10.1021/jacs.2c03607 |
| بيانات النشر: | American Chemical Society (ACS), 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | METAL-CATALYZED OXIDATION, Amyloid, Amyloid/chemistry, Biophysics, Biochemistry and Molecular Biology, Parkinson Disease, General Chemistry, Parkinson Disease/metabolism, Biochemistry, Biofysik, Catalysis, alpha-Synuclein/chemistry, Colloid and Surface Chemistry, OLIGOMERS, Structural Biology, BINDING, alpha-Synuclein, Humans, Tyrosine, FIBRILLATION, Tyrosine/analogs & derivatives, COPPER(II), Biokemi och molekylärbiologi, Strukturbiologi |
| الوصف: | 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. |
| وصف الملف: | application/pdf |
| تدمد: | 1520-5126 0002-7863 |
| DOI: | 10.1021/jacs.2c03607 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7a12848347027ec45af73136d3afcb59 https://doi.org/10.1021/jacs.2c03607 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....7a12848347027ec45af73136d3afcb59 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15205126 00027863 |
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| DOI: | 10.1021/jacs.2c03607 |