Academic Journal
Aromaticity at position 39 in α‐synuclein: A modulator of amyloid fibril assembly and membrane‐bound conformations
العنوان: | Aromaticity at position 39 in α‐synuclein: A modulator of amyloid fibril assembly and membrane‐bound conformations |
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المؤلفون: | 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. |
سنة النشر: | 2022 |
المجموعة: | Georg-August-Universität Göttingen: GoeScholar |
الوصف: | 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. ; 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 |
نوع الوثيقة: | article in journal/newspaper |
اللغة: | English |
تدمد: | 0961-8368 1469-896X |
Relation: | EXC 2067: Multiscale Bioimaging; SFB 1286: Quantitative Synaptologie; SFB 1286 %7C B08: Definition von Kaskaden molekularer Veränderungen bei Synucleinopathien während der Neurodegeneration; RG Griesinger; RG Outeiro (Experimental Neurodegeneration); https://resolver.sub.uni-goettingen.de/purl?gro-2/112073; https://mbexc.uni-goettingen.de/literature/publications/509; https://sfb1286.uni-goettingen.de/literature/publications/168 |
DOI: | 10.1002/pro.4360 |
الاتاحة: | https://resolver.sub.uni-goettingen.de/purl?gro-2/112073 https://doi.org/10.1002/pro.4360 https://mbexc.uni-goettingen.de/literature/publications/509 https://sfb1286.uni-goettingen.de/literature/publications/168 |
Rights: | CC BY-NC 4.0 ; http://creativecommons.org/licenses/by-nc/4.0/ |
رقم الانضمام: | edsbas.15F3F0C3 |
قاعدة البيانات: | BASE |
تدمد: | 09618368 1469896X |
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DOI: | 10.1002/pro.4360 |