Self-Replication of Prion Protein Fragment 89-230 Amyloid Fibrils Accelerated by Prion Protein Fragment 107-143 Aggregates.

Abstract

Prion protein amyloid aggregates are associated with infectious neurodegenerative diseases, known as transmissible spongiform encephalopathies. Self-replication of amyloid structures by refolding of native protein molecules is the probable mechanism of disease transmission. Amyloid fibril formation and self-replication can be affected by many different factors, including other amyloid proteins and peptides. Mouse prion protein fragments 107-143 (PrP(107-143)) and 89-230 (PrP(89-230)) can form amyloid fibrils. β-sheet core in PrP(89-230) amyloid fibrils is limited to residues ∼160-220 with unstructured N-terminus. We employed chemical kinetics tools, atomic force microscopy and Fourier-transform infrared spectroscopy, to investigate the effects of mouse prion protein fragment 107-143 fibrils on the aggregation of PrP(89-230). The data suggest that amyloid aggregates of a short prion-derived peptide are not able to seed PrP(89-230) aggregation; however, they accelerate the self-replication of PrP(89-230) amyloid fibrils. We conclude that PrP(107-143) fibrils could facilitate the self-replication of PrP(89-230) amyloid fibrils in several possible ways, and that this process deserves more attention as it may play an important role in amyloid propagation.

• Authors: Tomas Sneideris, Mantas Ziaunys, Brett K-Y Chu, Rita P-Y Chen, Vytautas Smirnovas
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 21 Issue 19 (Oct 08 2020) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 33049945 (Publication Type: Journal Article)

Chemical References

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

Topics

• Amyloid (chemistry)
• Animals
• Mice
• Microscopy, Atomic Force
• Peptide Fragments (chemistry)
• Prion Diseases (pathology)
• Prion Proteins (chemistry)
• Prions (chemistry)
• Protein Aggregates
• Protein Aggregation, Pathological
• Protein Conformation, beta-Strand
• Recombinant Proteins (chemistry)
• Spectroscopy, Fourier Transform Infrared