Determining the Location of the α-Synuclein Dimer Interface Using Native Top-Down Fragmentation and Isotope Depletion-Mass Spectrometry
| العنوان: | Determining the Location of the α-Synuclein Dimer Interface Using Native Top-Down Fragmentation and Isotope Depletion-Mass Spectrometry |
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| المؤلفون: | Kiani Jeacock, Alexandre Chappard, Kelly J. Gallagher, C. Logan Mackay, David P. A. Kilgour, Mathew H. Horrocks, Tilo Kunath, David J. Clarke |
| المصدر: | Jeacock, K, Chappard, A, Gallagher, K J, Mackay, C L, Kilgour, D P A, Horrocks, M H, Kunath, T & Clarke, D J 2023, ' Determining the location of the α-synuclein dimer Interface using native top-down fragmentation and isotope depletion-mass spectrometry ', Journal of the American Society for Mass Spectrometry . https://doi.org/10.1021/jasms.2c00339 |
| بيانات النشر: | American Chemical Society (ACS), 2023. |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Structural Biology, Spectroscopy |
| الوصف: | α-Synuclein (αSyn), a 140-residue intrinsically disordered protein, comprises the primary proteinaceous component of pathology-associated Lewy body inclusions in Parkinson’s disease (PD). Due to its association with PD, αSyn is studied extensively; however, the endogenous structure and physiological roles of this protein are yet to be fully understood. Here, ion mobility-mass spectrometry and native top-down electron capture dissociation fragmentation have been used to elucidate the structural properties associated with a stable, naturally occurring dimeric species of αSyn. This stable dimer appears in both wild-type (WT) αSyn and the PD-associated variant A53E. Furthermore, we integrated a novel method for generating isotopically depleted protein into our native top-down workflow. Isotope depletion increases signal-to-noise ratio and reduces the spectral complexity of fragmentation data, enabling the monoisotopic peak of low abundant fragment ions to be observed. This enables the accurate and confident assignment of fragments unique to the αSyn dimer to be assigned and structural information about this species to be inferred. Using this approach, we were able to identify fragments unique to the dimer, which demonstrates a C-terminal to C-terminal interaction between the monomer subunits. The approach in this study holds promise for further investigation into the structural properties of endogenous multimeric species of αSyn. |
| وصف الملف: | application/pdf |
| تدمد: | 1879-1123 1044-0305 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7f582ef9311fb2bc90e083331e48a6e1 https://doi.org/10.1021/jasms.2c00339 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....7f582ef9311fb2bc90e083331e48a6e1 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. 
Find this issue from the American Chemical Society | تدمد: | 18791123 10440305 |
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