Rapid degradation kinetics of amyloid fibrils under mild conditions by an archaeal chaperonin

Amyloid depositions containing exceptionally stable β-sheet rich protein aggregates, called fibrils are associated with prevalent and incurable neurodegenerative diseases. Chaperones are proteins that facilitate protein folding in both eukaryotes and prokaryotes. We found that a cold-adapted mutant ATP-dependant chaperonins (Hsp60) from a hyperthermophilic archaeon binds to and fragments insulin fibrils very rapidly with local targeted entry points. Individual fragments swell and the fibrillar β-sheet is quickly transformed into a mix of α-helical and unordered protein structures. After further incubation, the fragments coalesced, forming large amorphous aggregates with poly-disperse topologies. This finding represents a new approach to the disassembly of refractory protein aggregates under physiological conditions.

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► Chaperonin from hyperthermophile Pyrococcus furiosus degrades insulin fibrils.
► Hsp60 binds to and fragments amyloid fibrils at patterned intervals.
► Prolonged incubation with chaperonin produces polydisperse topologies.
► No cleavage of insulin polypeptide chains occurs when fibrils are degraded by Hsp60.