Four-component protein nanocages designed by programmed symmetry breaking
Four, eight or twenty C3 symmetric protein trimers can be arranged with tetrahedral, octahedral or icosahedral point group symmetry to generate closed cage-like structures<sup>1,2</sup>. Viruses access more complex higher triangulation number icosahedral architectures by breaking perfect point group symmetry<sup>3-9</sup>, 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 candidates<sup>10,11</sup> and targeted delivery vehicles<sup>12,13</sup>.
Authors
- Ryan D. Kibler (ORCID: https://orcid.org/0000-0001-6984-9887)
- Buwei Huang (ORCID: https://orcid.org/0000-0002-0762-7178)
- Madison Kennedy (ORCID: https://orcid.org/0000-0003-3422-9172)
- Yang Hsia (ORCID: https://orcid.org/0000-0001-7467-8373)
- Andrew J. Borst (ORCID: https://orcid.org/0000-0003-4297-7824)
- David A. Baker (ORCID: https://orcid.org/0000-0001-7896-6217)
- Green Ahn (ORCID: https://orcid.org/0000-0003-3086-4849)
- Barry Stoddard (ORCID: https://orcid.org/0000-0003-2250-9601)
- Annika Philomin (ORCID: https://orcid.org/0009-0008-0305-9709)
- Sangmin Lee (ORCID: https://orcid.org/0000-0002-1145-4708)
Institutions
- Pohang University of Science and Technology (KR)
- Howard Hughes Medical Institute (US)
- University of Washington (US)
- Fred Hutch Cancer Center (US)
- PDL BioPharma (United States) (US)
Publication Details
- Journal
- Nature
- Published
- 2024-12-18
- DOI
- https://doi.org/10.1038/s41586-024-07814-1
- Citations
- 38
- Primary Topic
- Bacteriophages and microbial interactions
- Type
- article
- Field-Weighted Citation Impact
- 17.44
Funders
- U.S. Department of Energy
- Bill and Melinda Gates Foundation
- Ohio State University
- Open Philanthropy Project
- National Energy Research Scientific Computing Center
- National Research Foundation
- National Research Foundation of Korea
- Ministry of Science and ICT, South Korea
- National Institutes of Health
- Defense Advanced Research Projects Agency
- Office of Science
- Advanced Research Projects Agency
- Basic Energy Sciences
- Biological and Environmental Research
- Lawrence Berkeley National Laboratory