Mechanisms of Strain Diversity of Disease-Associated in-Register Parallel β-Sheet Amyloids and Implications About Prion Strains
The mechanism of prion strain diversity remains unsolved. Investigation of inheritance and diversification of protein-based pathogenic information demands the identification of the detailed structures of abnormal isoforms of the prion protein (PrP<sup>Sc</sup>); however, achieving purifi...
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doaj-175de82862214fcda1bdf04ab29fd3492020-11-25T01:01:12ZengMDPI AGViruses1999-49152019-01-0111211010.3390/v11020110v11020110Mechanisms of Strain Diversity of Disease-Associated in-Register Parallel β-Sheet Amyloids and Implications About Prion StrainsYuzuru Taguchi0Hiroki Otaki1Noriyuki Nishida2Division of Cellular and Molecular Biology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523, JapanCenter for Bioinformatics and Molecular Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523, JapanDivision of Cellular and Molecular Biology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523, JapanThe mechanism of prion strain diversity remains unsolved. Investigation of inheritance and diversification of protein-based pathogenic information demands the identification of the detailed structures of abnormal isoforms of the prion protein (PrP<sup>Sc</sup>); however, achieving purification is difficult without affecting infectivity. Similar prion-like properties are recognized also in other disease-associated in-register parallel β-sheet amyloids including Tau and α-synuclein (αSyn) amyloids. Investigations into structures of those amyloids via solid-state nuclear magnetic resonance spectroscopy and cryo-electron microscopy recently made remarkable advances due to their relatively small sizes and lack of post-translational modifications. Herein, we review advances regarding pathogenic amyloids, particularly Tau and αSyn, and discuss implications about strain diversity mechanisms of prion/PrP<sup>Sc</sup> from the perspective that PrP<sup>Sc</sup> is an in-register parallel β-sheet amyloid. Additionally, we present our recent data of molecular dynamics simulations of αSyn amyloid, which suggest significance of compatibility between β-sheet propensities of the substrate and local structures of the template for stability of amyloid structures. Detailed structures of αSyn and Tau amyloids are excellent models of pathogenic amyloids, including PrP<sup>Sc</sup>, to elucidate strain diversity and pathogenic mechanisms.https://www.mdpi.com/1999-4915/11/2/110α-synucleintauamyloidprionprion proteinstrain diversitymolecular dynamics simulationsecondary structure predictionβ-archin-register parallel β-sheet |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yuzuru Taguchi Hiroki Otaki Noriyuki Nishida |
spellingShingle |
Yuzuru Taguchi Hiroki Otaki Noriyuki Nishida Mechanisms of Strain Diversity of Disease-Associated in-Register Parallel β-Sheet Amyloids and Implications About Prion Strains Viruses α-synuclein tau amyloid prion prion protein strain diversity molecular dynamics simulation secondary structure prediction β-arch in-register parallel β-sheet |
author_facet |
Yuzuru Taguchi Hiroki Otaki Noriyuki Nishida |
author_sort |
Yuzuru Taguchi |
title |
Mechanisms of Strain Diversity of Disease-Associated in-Register Parallel β-Sheet Amyloids and Implications About Prion Strains |
title_short |
Mechanisms of Strain Diversity of Disease-Associated in-Register Parallel β-Sheet Amyloids and Implications About Prion Strains |
title_full |
Mechanisms of Strain Diversity of Disease-Associated in-Register Parallel β-Sheet Amyloids and Implications About Prion Strains |
title_fullStr |
Mechanisms of Strain Diversity of Disease-Associated in-Register Parallel β-Sheet Amyloids and Implications About Prion Strains |
title_full_unstemmed |
Mechanisms of Strain Diversity of Disease-Associated in-Register Parallel β-Sheet Amyloids and Implications About Prion Strains |
title_sort |
mechanisms of strain diversity of disease-associated in-register parallel β-sheet amyloids and implications about prion strains |
publisher |
MDPI AG |
series |
Viruses |
issn |
1999-4915 |
publishDate |
2019-01-01 |
description |
The mechanism of prion strain diversity remains unsolved. Investigation of inheritance and diversification of protein-based pathogenic information demands the identification of the detailed structures of abnormal isoforms of the prion protein (PrP<sup>Sc</sup>); however, achieving purification is difficult without affecting infectivity. Similar prion-like properties are recognized also in other disease-associated in-register parallel β-sheet amyloids including Tau and α-synuclein (αSyn) amyloids. Investigations into structures of those amyloids via solid-state nuclear magnetic resonance spectroscopy and cryo-electron microscopy recently made remarkable advances due to their relatively small sizes and lack of post-translational modifications. Herein, we review advances regarding pathogenic amyloids, particularly Tau and αSyn, and discuss implications about strain diversity mechanisms of prion/PrP<sup>Sc</sup> from the perspective that PrP<sup>Sc</sup> is an in-register parallel β-sheet amyloid. Additionally, we present our recent data of molecular dynamics simulations of αSyn amyloid, which suggest significance of compatibility between β-sheet propensities of the substrate and local structures of the template for stability of amyloid structures. Detailed structures of αSyn and Tau amyloids are excellent models of pathogenic amyloids, including PrP<sup>Sc</sup>, to elucidate strain diversity and pathogenic mechanisms. |
topic |
α-synuclein tau amyloid prion prion protein strain diversity molecular dynamics simulation secondary structure prediction β-arch in-register parallel β-sheet |
url |
https://www.mdpi.com/1999-4915/11/2/110 |
work_keys_str_mv |
AT yuzurutaguchi mechanismsofstraindiversityofdiseaseassociatedinregisterparallelbsheetamyloidsandimplicationsaboutprionstrains AT hirokiotaki mechanismsofstraindiversityofdiseaseassociatedinregisterparallelbsheetamyloidsandimplicationsaboutprionstrains AT noriyukinishida mechanismsofstraindiversityofdiseaseassociatedinregisterparallelbsheetamyloidsandimplicationsaboutprionstrains |
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1725210215615299584 |