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

Biochem Biophys Res Commun. 2012 May 25;422(1):97-102. doi: 10.1016/j.bbrc.2012.04.113. Epub 2012 Apr 30.

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amyloid / chemistry*
  • Animals
  • Archaeal Proteins / chemistry*
  • Cattle
  • Chaperonin 60 / chemistry*
  • Insulins / chemistry*
  • Kinetics
  • Protein Structure, Secondary
  • Proteolysis*
  • Pyrococcus furiosus / metabolism*

Substances

  • Amyloid
  • Archaeal Proteins
  • Chaperonin 60
  • Insulins