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

ABSTRACT: 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, mod

SUBMITTER: Ukmar-Godec T 

PROVIDER: S-EPMC7439447 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature