title: Rapid degradation kinetics of amyloid fibrils under mild conditions by an archaeal chaperonin.
abstract: 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.
authors.affiliation: University at Albany, State University of New York, 1400 Washington Avenue, Albany, NY 12222, USA.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Kurouski
authors.forename: Haibin
authors.initials: H
authors.lastname: Luo
authors.forename: Valentin
authors.initials: V
authors.lastname: Sereda
authors.forename: Frank T
authors.initials: FT
authors.lastname: Robb
authors.forename: Igor K
authors.initials: IK
authors.lastname: Lednev
mesh_terms: D000682:Amyloid / Q000737:chemistry*; D000818:Animals; D019843:Archaeal Proteins / Q000737:chemistry*; D002417:Cattle; D018834:Chaperonin 60 / Q000737:chemistry*; D061385:Insulins / Q000737:chemistry*; D007700:Kinetics; D017433:Protein Structure, Secondary; D059748:Proteolysis; D020027:Pyrococcus furiosus / Q000378:metabolism*
chemical_list: D000682:Amyloid; D019843:Archaeal Proteins; D018834:Chaperonin 60; D061385:Insulins