Recent advances in protein design have ushered in an era of constructing intricate higher-order structures. Despite this progress, orchestrating the assembly of diverse protein units into cohesive artificial structures akin to biological assembly systems, especially in tubular forms, remains an elusive goal. To address this, we introduce the Nature-Inspired Protein Assembly Design (NIPAD), a novel methodology that 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 were incorporated into tubular assemblies, thereby enriching their structural diversity. Remarkably, these assemblies can be reversibly disassembled and reassembled in response to environmental stimuli, such as changes in salt concentration and temperature, mirroring the dynamic behaviour of natural systems. NIPAD 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 pioneering new applications.

中文翻译：

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细胞骨架等二元管状组件的蛋白质设计

蛋白质设计的最新进展开创了构建复杂高阶结构的时代。尽管取得了这些进展，将不同蛋白质单元组装成类似于生物组装系统的有粘性的人工结构，特别是管状形式，仍然是一个难以实现的目标。为了解决这个问题，我们引入了自然启发的蛋白质组装设计（NIPAD），这是一种新颖的方法，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。这些结构表现出类似于肌动蛋白丝的动态灵活性，冷冻电子显微镜揭示了不同的形态，如微管。通过模仿肌动蛋白丝，螺旋构象被纳入管状组件中，从而丰富了它们的结构多样性。值得注意的是，这些组件可以响应环境刺激（例如盐浓度和温度的变化）可逆地拆卸和重新组装，从而反映了自然系统的动态行为。 NIPAD 将合理的蛋白质设计与生物物理学见解相结合，从而创建仿生、适应性强和可逆的高阶组装体。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开拓新的应用具有重要意义。