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Recent progress on understanding the mechanisms of amyloid nucleation

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Abstract

Amyloid fibrils are supramolecular protein assemblies with a fibrous morphology and cross-β structure. The formation of amyloid fibrils typically follows a nucleation-dependent polymerization mechanism, in which a one-step nucleation scheme has widely been accepted. However, a variety of oligomers have been identified in early stages of fibrillation, and a nucleated conformational conversion (NCC) mechanism, in which oligomers serve as a precursor of amyloid nucleation and convert to amyloid nuclei, has been proposed. This development has raised the need to consider more complicated multi-step nucleation processes in addition to the simplest one-step process, and evidence for the direct involvement of oligomers as nucleation precursors has been obtained both experimentally and theoretically. Interestingly, the NCC mechanism has some analogy with the two-step nucleation mechanism proposed for inorganic and organic crystals and protein crystals, although a more dramatic conformational conversion of proteins should be considered in amyloid nucleation. Clarifying the properties of the nucleation precursors of amyloid fibrils in detail, in comparison with those of crystals, will allow a better understanding of the nucleation of amyloid fibrils and pave the way to develop techniques to regulate it.

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Acknowledgements

We wish to express our congratulations to Professor Fumio Arisaka on his 70th birthday, and we thank the editors for the great opportunity to participate in this special issue. We thank Dr. Hiroshi Imamura (Ritsumeikan Universiy) for his helpful comments and discussions on the earlier draft of this article. This work was supported by JSPS KAKENHI Grant Numbers JP16H04778, JP16H00772, JP16K17783, and JP17H06352.

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  1. Graduate School of Science, Kobe University, 1-1 Rokkodai, Nada, Kobe, Hyogo, 657-8501, Japan

    Eri Chatani & Naoki Yamamoto

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  1. Eri Chatani
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  2. Naoki Yamamoto
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Correspondence to Eri Chatani.

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Eri Chatani declares that she has no conflicts of interest. Naoki Yamamoto declares that he has no conflicts of interest.

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This article is part of a Special Issue on ‘Biomolecules to Bio-nanomachines—Fumio Arisaka 70th Birthday’ edited by Damien Hall, Junichi Takagi and Haruki Nakamura.

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Chatani, E., Yamamoto, N. Recent progress on understanding the mechanisms of amyloid nucleation. Biophys Rev 10, 527–534 (2018). https://doi.org/10.1007/s12551-017-0353-8

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