Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Abstract

Recent advances in protein design have ushered in an era of constructing intricate higher-order structures. Nonetheless, orchestrating the assembly of diverse protein units into cohesive artificial structures akin to biological assembly systems, especially in tubular forms, remains elusive. To this end, we develop a methodology inspired by nature, which utilises two distinct protein units to create unique tubular structures under carefully designed conditions. These structures demonstrate dynamic flexibility similar to that of actin filaments, with cryo electron microscopy revealing diverse morphologies, like microtubules. By mimicking actin filaments, helical conformations are incorporated into tubular assemblies, thereby enriching their structural diversity. Notably, these assemblies can be reversibly disassembled and reassembled in response to environmental stimuli, including changes in salt concentration and temperature, mirroring the dynamic behaviour of natural systems. This methodology combines rational protein design with biophysical insights, leading to the creation of biomimetic, adaptable, and reversible higher-order assemblies. This approach deepens our understanding of protein assembly design and complex biological structures. Concurrently, it broadens the horizons of synthetic biology and material science, holding significant implications for unravelling life’s fundamental processes and enabling future applications.

DOI： 10.1038/s41467-025-62076-3

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Other Link： https://www.nature.com/articles/s41467-025-62076-3

Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Abstract

Dialysis-related amyloidosis (DRA), a serious complication among long-term hemodialysis patients, is caused by amyloid fibrils of β2-microglobulin (β2m). Although high serum β2m levels and a long dialysis vintage are the primary and secondary risk factors for the onset of DRA, respectively, patients with these do not always develop DRA, indicating that there are additional risk factors. To clarify these unknown factors, we investigate the effects of human sera on β2m amyloid fibril formation, revealing that sera markedly inhibit amyloid fibril formation. Results from over 100 sera indicate that, although the inhibitory effects of sera deteriorate in long-term dialysis patients, they are ameliorated by maintenance dialysis treatments in the short term. Serum albumin prevents amyloid fibril formation based on macromolecular crowding effects, and decreased serum albumin concentration in dialysis patients is a tertiary risk factor for the onset of DRA. We construct a theoretical model assuming cumulative effects of the three risk factors, suggesting the importance of monitoring temporary and accumulated risks to prevent the development of amyloidosis, which occurs based on supersaturation-limited amyloid fibril formation in a crowded milieu.

DOI： 10.1038/s41467-022-33247-3

PubMed

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Other Link： https://www.nature.com/articles/s41467-022-33247-3

Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Abstract

The thermodynamic hypothesis of protein folding, known as the “Anfinsen’s dogma” states that the native structure of a protein represents a free energy minimum determined by the amino acid sequence. However, inconsistent with the Anfinsen’s dogma, globular proteins can misfold to form amyloid fibrils, which are ordered aggregates associated with diseases such as Alzheimer’s and Parkinson’s diseases. Here, we present a general concept for the link between folding and misfolding. We tested the accessibility of the amyloid state for various proteins upon heating and agitation. Many of them showed Anfinsen-like reversible unfolding upon heating, but formed amyloid fibrils upon agitation at high temperatures. We show that folding and amyloid formation are separated by the supersaturation barrier of a protein. Its breakdown is required to shift the protein to the amyloid pathway. Thus, the breakdown of supersaturation links the Anfinsen’s intramolecular folding universe and the intermolecular misfolding universe.

DOI： 10.1038/s42003-020-01641-6

PubMed

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Other Link： https://www.nature.com/articles/s42003-020-01641-6

DOI： 10.1101/2025.11.24.689909

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Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

The supersaturation of a solution refers to a non-equilibrium phase in which the solution is trapped in a soluble state, even though the solute’s concentration is greater than its thermodynamic solubility. Upon breaking supersaturation, crystals form and the concentration of the solute decreases to its thermodynamic solubility. Soon after the discovery of the prion phenomena, it was recognized that prion disease transmission and propagation share some similarities with the process of crystallization. Subsequent studies exploring the structural and functional association between amyloid fibrils and amyloidoses solidified this paradigm. However, recent studies have not necessarily focused on supersaturation, possibly because of marked advancements in structural studies clarifying the atomic structures of amyloid fibrils. On the other hand, there is increasing evidence that supersaturation plays a critical role in the formation of amyloid fibrils and the onset of amyloidosis. Here, we review the recent evidence that supersaturation plays a role in linking unfolding/folding and amyloid fibril formation. We also introduce the HANABI (HANdai Amyloid Burst Inducer) system, which enables high-throughput analysis of amyloid fibril formation by the ultrasonication-triggered breakdown of supersaturation. In addition to structural studies, studies based on solubility and supersaturation are essential both to developing a comprehensive understanding of amyloid fibrils and their roles in amyloidosis, and to developing therapeutic strategies.

DOI： 10.3390/molecules27144588

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Total pages：xi, 402p   Language：Japanese  

CiNii Books

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Event date： 2026.6

Presentation type：Oral presentation (invited, special)  

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Application no：特願2024-65760  Date applied：2024.4

Announcement no：特開2025-162451  Date announced：2025.10

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Award type：Award from Japanese society, conference, symposium, etc.  Country：Japan

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https://groups.oist.jp/img/amed

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