DnaJB1 chaperone inhibits tau aggregation by recognizing its N-terminus.

ABSTRACT: A network of protein folding and degradation machineries maintains protein homeostasis by preventing the accumulation of misfolded proteins and by facilitating their clearance. These systems are also crucial for the inhibition of protein aggregation in neurodegenerative diseases where misfolded proteins often aggregate into β-rich amyloid fibrils. How these machineries selectively recognize pathological aggregates over normal conformations remains unclear. Here, we present the molecular logic for how a Hsp70 co-chaperone from the J-domain protein family, DnaJB1, binds pathological aggregates of the microtubule-associated protein tau through the recognition of the flexible N-terminus that comprises the disordered fuzzy coat of fibrils. We show that this interaction contributes to the regula

SUBMITTER: Wydorski PM 

PROVIDER: S-EPMC12621901 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature