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bioRxiv · 10.1101/2023.06.16.545341

Design of four component T=4 tetrahedral, octahedral, and icosahedral protein nanocages through programmed symmetry breaking

Lee, S.·Kibler, R. D.·Hsia, Y.·Borst, A. J.·Philomin, A.·Kennedy, M. A.·Stoddard, B. L.·Baker, D.
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Abstract

Four, eight or twenty C3 symmetric protein trimers can be arranged with tetrahedral (T-sym), octahedral (O-sym) or icosahedral (I-sym) point group symmetry to generate closed cage-like structures1,2. Generating more complex closed structures requires breaking perfect point group symmetry. Viruses do this in the icosahedral case using quasi-symmetry or pseudo-symmetry to access higher triangulation number architectures3-9, but nature appears not to have explored higher triangulation number tetrahedral or octahedral symmetries. Here, we describe a general design strategy for building T = 4 architectures starting from simpler T = 1 structures through pseudo-symmetrization of trimeric building blocks. Electron microscopy confirms the structures of T = 4 cages with 48 (T-sym), 96 (O-sym), and 240 (I-sym) subunits, each with four distinct chains and six different protein-protein interfaces, and diameters of 33nm, 43nm, and 75nm, 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.

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Lee, S., Kibler, R. D., Hsia, Y., Borst, A. J., Philomin, A., Kennedy, M. A., Stoddard, B. L., Baker, D.. 2023-06-17. Design of four component T=4 tetrahedral, octahedral, and icosahedral protein nanocages through programmed symmetry breaking. https://doi.org/10.1101/2023.06.16.545341

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