%0 Journal Article
%A Ukmar-Godec, Tina
%A Fang, P.
%A Ibanez de Opakua, Alain
%A Henneberg, F.
%A Godec, A.
%A Pan, K.-T.
%A Cima Omori, Maria Sol
%A Chari, A.
%A Mandelkow, Eckhard
%A Urlaub, H.
%A Zweckstetter, Markus
%T Proteasomal degradation of the intrinsically disordered protein tau at single-residue resolution
%J Science advances
%V 6
%N 30
%@ 2375-2548
%C Washington, DC [u.a.]
%I Assoc.
%M DZNE-2020-01280
%P eaba3916 -
%D 2020
%X 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%2 pmc:PMC7439447
%$ pmid:32832664
%R 10.1126/sciadv.aba3916
%U https://pub.dzne.de/record/153283