Proteasomal degradation of the intrinsically disordered protein tau at single-residue resolution
| العنوان: | Proteasomal degradation of the intrinsically disordered protein tau at single-residue resolution |
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| المؤلفون: | Henning Urlaub, Tina Ukmar-Godec, Aljaž Godec, Ashwin Chari, Eckhard Mandelkow, Markus Zweckstetter, Pan Fang, A. Ibanez de Opakua, M-S Cima-Omori, Fabian Henneberg, K-T Pan |
| المصدر: | Science advances 6(30), eaba3916-(2020). doi:10.1126/sciadv.aba3916 Science Advances |
| بيانات النشر: | American Association for the Advancement of Science (AAAS), 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0303 health sciences, Multidisciplinary, biology, Degradation kinetics, Chemistry, Kinase, Tau protein, Biophysics, SciAdv r-articles, Cleavage (embryo), Intrinsically disordered proteins, Protein kinase II, 03 medical and health sciences, 0302 clinical medicine, mental disorders, biology.protein, Posttranslational modification, Phosphorylation, ddc:500, Research Articles, 030217 neurology & neurosurgery, Research Article, Neuroscience, 030304 developmental biology |
| الوصف: | Dissecting the degradation of the Alzheimer’s disease–related protein Tau by the 20S proteasome at single-residue resolution. Intrinsically disordered proteins (IDPs) can be degraded in a ubiquitin-independent process by the 20S proteasome. Decline in 20S activity characterizes neurodegenerative diseases. Here, we examine 20S degradation of IDP tau, a protein that aggregates into insoluble deposits in Alzheimer’s disease. We show that cleavage of tau by the 20S proteasome is most efficient within the aggregation-prone repeat region of tau and generates both short, aggregation-deficient peptides and two long fragments containing residues 1 to 251 and 1 to 218. Phosphorylation of tau by the non-proline–directed Ca2+/calmodulin-dependent protein kinase II inhibits degradation by the 20S proteasome. Phosphorylation of tau by GSK3β, a major proline-directed tau kinase, modulates tau degradation kinetics in a residue-specific manner. The study provides detailed insights into the degradation products of tau generated by the 20S proteasome, the residue specificity of degradation, single-residue degradation kinetics, and their regulation by posttranslational modification. |
| وصف الملف: | application/pdf |
| تدمد: | 2375-2548 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0fb81fa9d7a674dd41dd112a237bd979 https://doi.org/10.1126/sciadv.aba3916 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....0fb81fa9d7a674dd41dd112a237bd979 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23752548 |
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