Four-component protein nanocages designed by programmed symmetry breaking

• 成果类型: Article
• 署名作者: Lee, Sangmin; Kibler, Ryan D.; Ahn, Green; Hsia, Yang; Borst, Andrew J.; Philomin, Annika; Kennedy, Madison A.; Huang, Buwei; Stoddard, Barry; Baker, David
• 署名单位: University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; Howard Hughes Medical Institute; Pohang University of Science & Technology (POSTECH); Fred Hutchinson Cancer Center
• 刊物名称: Nature
• ISSN/ISSBN: 0028-2293
• DOI: 10.1038/s41586-024-07814-1
• 发表日期: 2025-02-13
• 关键词: computational design; cage

摘要

Four, eight or twenty C3 symmetric protein trimers can be arranged with tetrahedral, octahedral or icosahedral point group symmetry to generate closed cage-like structures1,2. Viruses access more complex higher triangulation number icosahedral architectures by breaking perfect point group symmetry3, 4, 5, 6, 7, 8-9, but nature appears not to have explored similar symmetry breaking for tetrahedral or octahedral symmetries. Here we describe a general design strategy for building higher triangulation number architectures starting from regular polyhedra through pseudosymmetrization of trimeric building blocks. Electron microscopy confirms the structures of T = 4 cages with 48 (tetrahedral), 96 (octahedral) and 240 (icosahedral) subunits, each with 4 distinct chains and 6 different protein-protein interfaces, and diameters of 33 nm, 43 nm and 75 nm, respectively. Higher triangulation number viruses possess very sophisticated functionalities; our general route to higher triangulation number nanocages should similarly enable a next generation of multiple antigen-displaying vaccine candidates10,11 and targeted delivery vehicles12,13.