美国华盛顿大学Neil P. King课题组在研究中取得进展。他们完成了伪对称蛋白纳米笼的分层设计。2024年12月18日出版的《自然》杂志发表了这项成果。

据悉，生物系统中大量存在着，大小从数百千道尔顿到数百兆道尔顿不等的离散蛋白质组装体，其能执行高度专业化的功能。尽管最近在精确设计新的自组装蛋白质方面，取得了令人瞩目的进展，但这些组装体的大小和复杂性一直受到严格对称性的限制。

研究人员受到在细菌微腔和病毒外壳中观察到的假对称性特征启发，开发出一种分层计算方法，用于设计大型假对称自组装蛋白质纳米材料。研究通过计算设计了假对称异构体成分，并利用它们创建了具有二十面体对称性的离散笼状蛋白质组装体，其分布包含240、540和 960个亚基。

这些纳米笼的直径分别为49、71和96纳米，是迄今为止通过计算设计生成的最大的有界蛋白质组装体。更广泛地说，通过超越严格的对称性，该研究工作大大拓宽了可通过设计获得的自组装蛋白质结构的种类。

附：英文原文

Title: Hierarchical design of pseudosymmetric protein nanocages

Author: Dowling, Quinton M., Park, Young-Jun, Fries, Chelsea N., Gerstenmaier, Neil C., Ols, Sebastian, Yang, Erin C., Wargacki, Adam J., Dosey, Annie, Hsia, Yang, Ravichandran, Rashmi, Walkey, Carl D., Burrell, Anika L., Veesler, David, Baker, David, King, Neil P.

Issue&Volume: 2024-12-18

Abstract: 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 functions1,2. 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 96nm 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.

DOI: 10.1038/s41586-024-08360-6

Source: https://www.nature.com/articles/s41586-024-08360-6