Aromaticity at position 39 in α‐synuclein: A modulator of amyloid fibril assembly and membrane‐bound conformations
2022 | journal article; research paper. A publication with affiliation to the University of Göttingen.
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Aromaticity at position 39 in α‐synuclein: A modulator of amyloid fibril assembly and membrane‐bound conformations
Buratti, F. A.; Boeffinger, N.; Garro, H. A.; Flores, J. S.; Hita, F. J.; Gonçalves, P. do C. & Copello, F. dos R. et al. (2022)
Protein Science, 31(7). DOI: https://doi.org/10.1002/pro.4360
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Details
- Authors
- Buratti, Fiamma A.; Boeffinger, Nicola; Garro, Hugo A.; Flores, Jesica S.; Hita, Francisco J.; Gonçalves, Phelippe do Carmo; Copello, Federico dos Reis; Lizarraga, Leonardo; Rossetti, Giulia; Carloni, Paolo; Fernández, Claudio O.
- Abstract
- Recent studies revealed that molecular events related with the physiology and pathology of αS might be regulated by specific sequence motifs in the primary sequence of αS. The importance of individual residues in these motifs remains an important open avenue of investigation. In this work, we have addressed the structural details related to the amyloid fibril assembly and lipid-binding features of αS through the design of site-directed mutants at position 39 of the protein and their study by in vitro and in vivo assays. We demonstrated that aromaticity at position 39 of αS primary sequence influences strongly the aggregation properties and the membrane-bound conformations of the protein, molecular features that might have important repercussions for the function and dysfunction of αS. Considering that aggregation and membrane damage is an important driver of cellular toxicity in amyloid diseases, future work is needed to link our findings with studies based on toxicity and neuronal cell death.
- Issue Date
- 2022
- Journal
- Protein Science
- Project
- EXC 2067: Multiscale Bioimaging
SFB 1286: Quantitative Synaptologie
SFB 1286 | B08: Definition von Kaskaden molekularer Veränderungen bei Synucleinopathien während der Neurodegeneration - Working Group
- RG Griesinger
RG Outeiro (Experimental Neurodegeneration) - ISSN
- 0961-8368
- eISSN
- 1469-896X
- Language
- English
- Sponsor
- Michael J. Fox Foundation for Parkinson's Research https://doi.org/10.13039/100000864
Horizon 2020 Framework Programme https://doi.org/10.13039/100010661
Deutsche Forschungsgemeinschaft https://doi.org/10.13039/501100001659
Max-Planck-Gesellschaft https://doi.org/10.13039/501100004189
Universidad Nacional de Rosario https://doi.org/10.13039/100009573
Alexander von Humboldt-Stiftung https://doi.org/10.13039/100005156