Self-Replication of Prion Protein Fragment 89-230 Amyloid Fibrils Accelerated by Prion Protein Fragment 107-143 Aggregates
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...
Main Authors: | , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2020-10-01
|
Series: | International Journal of Molecular Sciences |
Subjects: | |
Online Access: | https://www.mdpi.com/1422-0067/21/19/7410 |
Summary: | 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. <inline-formula><math display="inline"><semantics><mi mathvariant="sans-serif">β</mi></semantics></math></inline-formula>-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. |
---|---|
ISSN: | 1661-6596 1422-0067 |