Department of Biochemistry, University of Washington, Seattle, WA, USA.
Institute for Protein Design, University of Washington, Seattle, WA, USA.
Nat Commun. 2021 Apr 16;12(1):2294. doi: 10.1038/s41467-021-22276-z.
A systematic and robust approach to generating complex protein nanomaterials would have broad utility. We develop a hierarchical approach to designing multi-component protein assemblies from two classes of modular building blocks: designed helical repeat proteins (DHRs) and helical bundle oligomers (HBs). We first rigidly fuse DHRs to HBs to generate a large library of oligomeric building blocks. We then generate assemblies with cyclic, dihedral, and point group symmetries from these building blocks using architecture guided rigid helical fusion with new software named WORMS. X-ray crystallography and cryo-electron microscopy characterization show that the hierarchical design approach can accurately generate a wide range of assemblies, including a 43 nm diameter icosahedral nanocage. The computational methods and building block sets described here provide a very general route to de novo designed protein nanomaterials.
一种系统而稳健的生成复杂蛋白质纳米材料的方法将具有广泛的用途。我们开发了一种从两类模块化构建块设计多组分蛋白质组装体的层次方法：设计的螺旋重复蛋白（DHRs）和螺旋束低聚物（HBs）。我们首先将 DHRs 刚性融合到 HBs 上，以生成一个大型寡聚构建块库。然后，我们使用名为 WORMS 的新软件，通过架构引导的刚性螺旋融合，从这些构建块中生成具有循环、二面角和点群对称性的组装体。X 射线晶体学和低温电子显微镜表征表明，层次设计方法可以准确地生成广泛的组装体，包括一个 43nm 直径的二十面体纳米笼。这里描述的计算方法和构建块集为从头设计的蛋白质纳米材料提供了一条非常通用的途径。
