Publisher：openRxiv  

The ability to rationally modulate the morphology of artificial higher-order protein assemblies remains limited, particularly for geometrically constrained architectures such as tubes. Here, we show that simple tuning of the interaction stability within a heterodimeric coiled-coil linker, guided by deep-learning-based predictions from ThermoMPNN, provides an effective strategy for programming the assembly behaviour of two-component protein tubes. By engineering a systematic stability gradient within the M3L2/p66α heterodimeric linker, we generated single-amino-acid variants that exhibit predictable shifts in the temperature window for tube formation and produce tubes with distinct diameters. Notably, the least stable variant uniquely accesses multilayered tube-in-tube architectures. Time-course electron microscopy reveals that these hierarchical structures arise through a sequential process involving the initial formation of thin tubes, subsequent wall thickening, and eventual development of nested tubes, highlighting the role of transient linker rearrangements near the thermal transition. Together, these findings establish coiled-coil stability as a minimal and tunable design parameter that governs higher-order morphology and offer a minimal and programmable framework for constructing rationally designed protein tube architectures.

DOI： 10.1101/2025.11.24.689909

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Publishing type：Research paper (scientific journal)  

DOI： 10.1038/s41467-025-62076-3

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Language：English   Publishing type：Research paper (scientific journal)  

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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Publishing type：Research paper (scientific journal)  

DOI： 10.3390/molecules27144588

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Publishing type：Research paper (scientific journal)  

DOI： 10.1038/s42003-020-01641-6

PubMed

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Total pages：xi, 402p   Language：Japanese  

CiNii Books

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

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