Academic Journal
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 |
|---|---|
| المؤلفون: | Ukmar-Godec, T., Fang, P., Ibáñez de Opakua, A., Henneberg, F., Godec, A., Pan, K., Cima-Omori, M., Chari, A., Mandelkow, E., Urlaub, H., Zweckstetter, M. |
| المصدر: | Science Advances |
| سنة النشر: | 2020 |
| المجموعة: | Max Planck Society: MPG.PuRe |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| Relation: | http://hdl.handle.net/21.11116/0000-0007-1736-3; http://hdl.handle.net/21.11116/0000-0007-173C-D; http://hdl.handle.net/21.11116/0000-0007-173D-C |
| الاتاحة: | http://hdl.handle.net/21.11116/0000-0007-1736-3 http://hdl.handle.net/21.11116/0000-0007-173C-D http://hdl.handle.net/21.11116/0000-0007-173D-C |
| Rights: | info:eu-repo/semantics/openAccess ; http://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: | edsbas.43EDD717 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |