Discrete protein assemblies ranging from hundreds of kilodaltons to hundreds of megadaltons in size are a ubiquitous feature of biological systems and perform highly specialized functions^1,2. Despite remarkable recent progress in accurately designing new self-assembling proteins, the size and complexity of these assemblies has been limited by a reliance on strict symmetry³. Here, inspired by the pseudosymmetry observed in bacterial microcompartments and viral capsids, we developed a hierarchical computational method for designing large pseudosymmetric self-assembling protein nanomaterials. We computationally designed pseudosymmetric heterooligomeric components and used them to create discrete, cage-like protein assemblies with icosahedral symmetry containing 240, 540 and 960 subunits. At 49, 71 and 96 nm diameter, these nanocages are the largest bounded computationally designed protein assemblies generated to date. More broadly, by moving beyond strict symmetry, our work substantially broadens the variety of self-assembling protein architectures that are accessible through design.

从数百千道尔顿到数百兆道尔顿大小的离散蛋白质组装体是生物系统无处不在的特征，并执行高度专业化的功能^1,2。尽管最近在准确设计新的自组装蛋白方面取得了显著进展，但这些组装的大小和复杂性一直受到严格对称性的限制³。在这里，受到在细菌微区室和病毒衣壳中观察到的伪对称性的启发，我们开发了一种分层计算方法，用于设计大型伪对称自组装蛋白质纳米材料。我们计算设计了伪对称异寡聚成分，并使用它们来创建离散的笼状蛋白质组装体，具有二十面体对称性，包含 240、540 和 960 个亚基。这些纳米笼的直径为 49、71 和 96 nm，是迄今为止生成的最大的有界计算设计蛋白质组装体。更广泛地说，通过超越严格的对称性，我们的工作大大拓宽了可通过设计访问的自组装蛋白质结构的多样性。