Noji Masahiro, Sugita Yukihiko, Yamazaki Yosuke, Miyazaki Makito, Suzuki Yuta
Research Fellow of Japan Society for the Promotion of Science, Tokyo, Japan.
Graduate School of Human and Environmental Studies, Kyoto University, Kyoto, Japan.
Nat Commun. 2025 Jul 22;16(1):6738. doi: 10.1038/s41467-025-62076-3.
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.
蛋白质设计的最新进展开启了构建复杂高阶结构的时代。然而，将不同的蛋白质单元组装成类似于生物组装系统的凝聚性人工结构，尤其是管状结构，仍然难以实现。为此，我们开发了一种受自然启发的方法，该方法利用两种不同的蛋白质单元在精心设计的条件下创建独特的管状结构。这些结构表现出与肌动蛋白丝相似的动态柔韧性，冷冻电子显微镜揭示了多种形态，如微管。通过模仿肌动蛋白丝，螺旋构象被纳入管状组装体中，从而丰富了它们的结构多样性。值得注意的是，这些组装体可以响应环境刺激，包括盐浓度和温度的变化，进行可逆的拆卸和重新组装，这反映了自然系统的动态行为。这种方法将合理的蛋白质设计与生物物理见解相结合，导致了仿生、适应性强和可逆的高阶组装体的创建。这种方法加深了我们对蛋白质组装设计和复杂生物结构的理解。同时，它拓宽了合成生物学和材料科学的视野，对揭示生命的基本过程和实现未来应用具有重要意义。
