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  Proteasomal degradation of the intrinsically disordered protein tau at single-residue resolution

Ukmar-Godec, T., Fang, P., Ibáñez de Opakua, A., Henneberg, F., Godec, A., Pan, K. T., et al. (2020). Proteasomal degradation of the intrinsically disordered protein tau at single-residue resolution. Science Advances, 6(30): eaba3916. doi:10.1126/sciadv.aba3916.

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Ukmar-Godec, T.1, Autor           
Fang, P.2, Autor           
Ibáñez de Opakua, A. , Autor
Henneberg, F.3, Autor           
Godec, A.4, Autor           
Pan, K. T.2, Autor           
Cima-Omori, M.-S., Autor
Chari, A.5, Autor           
Mandelkow, E., Autor
Urlaub, H.2, Autor           
Zweckstetter, M.1, Autor           
Affiliations:
1Research Group of Protein Structure Determination using NMR, MPI for Biophysical Chemistry, Max Planck Society, ou_578571              
2Research Group of Bioanalytical Mass Spectrometry, MPI for Biophysical Chemistry, Max Planck Society, ou_578613              
3Department of Structural Dynamics, MPI for Biophysical Chemistry, Max Planck Society, ou_2205645              
4Research Group of Mathematical Biophysics, MPI for Biophysical Chemistry, Max Planck Society, ou_2396692              
5Research Group of Structural Biochemistry and Mechanisms, MPI for Biophysical Chemistry, Max Planck Society, ou_3265855              

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 Zusammenfassung: 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.

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Sprache(n): eng - English
 Datum: 2020-07-22
 Publikationsstatus: Online veröffentlicht
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 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: DOI: 10.1126/sciadv.aba3916
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Titel: Science Advances
Genre der Quelle: Zeitschrift
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Seiten: 12 Band / Heft: 6 (30) Artikelnummer: eaba3916 Start- / Endseite: - Identifikator: -