Covalent structural changes in unfolded GroES that lead to amyloid fibril formation detected by NMR: Insight into intrinsically disordered proteins.
Covalent structural changes in unfolded GroES that lead to amyloid fibril formation detected by NMR: Insight into intrinsically disordered proteins.
J Biol Chem. 2011 Apr 20;
Authors: Iwasa H, Meshitsuka S, Hongo K, Mizobata T, Kawata Y
Co-chaperonin GroES from E. coli works with chaperonin GroEL to mediate the folding reactions of various proteins. However, under specific conditions, i. e., the completely disordered state in Gdn-HCl, this molecular chaperone forms amyloid fibrils similar to those observed in various neurodegenerative diseases. Thus, this is a good model system to understand the amyloid fibril formation mechanism of intrinsically disordered proteins. Here, we identified a critical intermediate of GroES in the early stages of this fibril formation using NMR and mass spectroscopy measurements. A covalent rearrangement of the polypeptide bond at Asn45-Gly46 and/or Asn51-Gly52 that eventually yield ?-aspartic acids via deamidation of asparagine was observed to precede fibril formation. Mutation of these asparagines to alanines resulted in delayed nucleus formation. Our results indicate that peptide bond rearrangement at Asn-Gly enhances the formation of GroES amyloid fibrils. The finding provides a novel insight into the structural process of amyloid fibril formation from a disordered state, which may be applicable to intrinsically disordered proteins in general.
PMID: 21507961 [PubMed - as supplied by publisher]
Source:
PubMed