Amyloid core formed of full-length recombinant mouse prion protein involves sequence 127-143 but not sequence 107-126

PLoS One. 2013 Jul 3;8(7):e67967. doi: 10.1371/journal.pone.0067967. Print 2013.

Abstract

The principal event underlying the development of prion disease is the conversion of soluble cellular prion protein (PrP(C)) into its disease-causing isoform, PrP(Sc). This conversion is associated with a marked change in secondary structure from predominantly α-helical to a high β-sheet content, ultimately leading to the formation of aggregates consisting of ordered fibrillar assemblies referred to as amyloid. In vitro, recombinant prion proteins and short prion peptides from various species have been shown to form amyloid under various conditions and it has been proposed that, theoretically, any protein and peptide could form amyloid under appropriate conditions. To identify the peptide segment involved in the amyloid core formed from recombinant full-length mouse prion protein mPrP(23-230), we carried out seed-induced amyloid formation from recombinant prion protein in the presence of seeds generated from the short prion peptides mPrP(107-143), mPrP(107-126), and mPrP(127-143). Our results showed that the amyloid fibrils formed from mPrP(107-143) and mPrP(127-143), but not those formed from mPrP(107-126), were able to seed the amyloidogenesis of mPrP(23-230), showing that the segment residing in sequence 127-143 was used to form the amyloid core in the fibrillization of mPrP(23-230).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amyloid / chemistry*
  • Amyloid / ultrastructure
  • Animals
  • Kinetics
  • Mice
  • Molecular Sequence Data
  • Peptide Fragments / chemistry*
  • Prion Proteins
  • Prions / chemistry*
  • Prions / genetics
  • Protein Folding
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics

Substances

  • Amyloid
  • Peptide Fragments
  • Prion Proteins
  • Prions
  • Prnp protein, mouse
  • Recombinant Proteins

Grants and funding

This work was supported by the Academia Sinica and the National Science Council, Taiwan, R. O. C. (grant nos. NSC 97-2321-B-001-032, NSC 98-2311-B-001-019, NSC 99-2321-B-001-038, and NSC 100-2321-B-001-026). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.