Conformational Variability of Amyloid-β and the Morphological Diversity of Its Aggregates
Protein folding is the most fundamental and universal example of biomolecular self-organization and is characterized as an intramolecular process. In contrast, amyloidogenic proteins can interact with one another, leading to protein aggregation. The energy landscape of amyloid fibril formation is ch...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-07-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/15/4787 |
| _version_ | 1797432768018251776 |
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| author | Maho Yagi-Utsumi Koichi Kato |
| author_facet | Maho Yagi-Utsumi Koichi Kato |
| author_sort | Maho Yagi-Utsumi |
| collection | DOAJ |
| description | Protein folding is the most fundamental and universal example of biomolecular self-organization and is characterized as an intramolecular process. In contrast, amyloidogenic proteins can interact with one another, leading to protein aggregation. The energy landscape of amyloid fibril formation is characterized by many minima for different competing low-energy structures and, therefore, is much more enigmatic than that of multiple folding pathways. Thus, to understand the entire energy landscape of protein aggregation, it is important to elucidate the full picture of conformational changes and polymorphisms of amyloidogenic proteins. This review provides an overview of the conformational diversity of amyloid-β (Aβ) characterized from experimental and theoretical approaches. Aβ exhibits a high degree of conformational variability upon transiently interacting with various binding molecules in an unstructured conformation in a solution, forming an α-helical intermediate conformation on the membrane and undergoing a structural transition to the β-conformation of amyloid fibrils. This review also outlines the structural polymorphism of Aβ amyloid fibrils depending on environmental factors. A comprehensive understanding of the energy landscape of amyloid formation considering various environmental factors will promote drug discovery and therapeutic strategies by controlling the fibril formation pathway and targeting the consequent morphology of aggregated structures. |
| first_indexed | 2024-03-09T10:06:28Z |
| format | Article |
| id | doaj.art-57e50d267c6d4645b3f7b9c5af2e67d5 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T10:06:28Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-57e50d267c6d4645b3f7b9c5af2e67d52023-12-01T23:03:03ZengMDPI AGMolecules1420-30492022-07-012715478710.3390/molecules27154787Conformational Variability of Amyloid-β and the Morphological Diversity of Its AggregatesMaho Yagi-Utsumi0Koichi Kato1Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, JapanGraduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, JapanProtein folding is the most fundamental and universal example of biomolecular self-organization and is characterized as an intramolecular process. In contrast, amyloidogenic proteins can interact with one another, leading to protein aggregation. The energy landscape of amyloid fibril formation is characterized by many minima for different competing low-energy structures and, therefore, is much more enigmatic than that of multiple folding pathways. Thus, to understand the entire energy landscape of protein aggregation, it is important to elucidate the full picture of conformational changes and polymorphisms of amyloidogenic proteins. This review provides an overview of the conformational diversity of amyloid-β (Aβ) characterized from experimental and theoretical approaches. Aβ exhibits a high degree of conformational variability upon transiently interacting with various binding molecules in an unstructured conformation in a solution, forming an α-helical intermediate conformation on the membrane and undergoing a structural transition to the β-conformation of amyloid fibrils. This review also outlines the structural polymorphism of Aβ amyloid fibrils depending on environmental factors. A comprehensive understanding of the energy landscape of amyloid formation considering various environmental factors will promote drug discovery and therapeutic strategies by controlling the fibril formation pathway and targeting the consequent morphology of aggregated structures.https://www.mdpi.com/1420-3049/27/15/4787aggregationamyloid-βcryo-electron microscopyfibrilgangliosidemolecular chaperone |
| spellingShingle | Maho Yagi-Utsumi Koichi Kato Conformational Variability of Amyloid-β and the Morphological Diversity of Its Aggregates Molecules aggregation amyloid-β cryo-electron microscopy fibril ganglioside molecular chaperone |
| title | Conformational Variability of Amyloid-β and the Morphological Diversity of Its Aggregates |
| title_full | Conformational Variability of Amyloid-β and the Morphological Diversity of Its Aggregates |
| title_fullStr | Conformational Variability of Amyloid-β and the Morphological Diversity of Its Aggregates |
| title_full_unstemmed | Conformational Variability of Amyloid-β and the Morphological Diversity of Its Aggregates |
| title_short | Conformational Variability of Amyloid-β and the Morphological Diversity of Its Aggregates |
| title_sort | conformational variability of amyloid β and the morphological diversity of its aggregates |
| topic | aggregation amyloid-β cryo-electron microscopy fibril ganglioside molecular chaperone |
| url | https://www.mdpi.com/1420-3049/27/15/4787 |
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