{"doi":"10.1101/2023.06.16.545341","title":"Design of four component T=4 tetrahedral, octahedral, and icosahedral protein nanocages through programmed symmetry breaking","abstract":"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 structures 1,2 . 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 architectures 3–9 , 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 candidates 10,11 and targeted delivery vehicles 12,13 .","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":392450,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9535,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":242357,"name":"Ryan D. Kibler","orcid":"0000-0001-6984-9887","position":1,"is_corresponding":false},{"id":557874,"name":"Yang Hsia","orcid":"0000-0001-7467-8373","position":2,"is_corresponding":false},{"id":357033,"name":"Andrew J. Borst","orcid":"0000-0003-4297-7824","position":3,"is_corresponding":false},{"id":1166002,"name":"Annika Philomin","orcid":"0009-0008-0305-9709","position":4,"is_corresponding":false},{"id":667585,"name":"Madison Kennedy","orcid":"0000-0003-3422-9172","position":5,"is_corresponding":false},{"id":429000,"name":"Barry Stoddard","orcid":"0000-0003-2250-9601","position":6,"is_corresponding":false},{"id":105706,"name":"David Baker","orcid":"0000-0001-7896-6217","position":7,"is_corresponding":false},{"id":1163623,"name":"Sangmin Lee","orcid":"0000-0002-1145-4708","position":0,"is_corresponding":true}],"reference_count":29,"raw_metadata":null,"created_at":"2026-07-19T01:18:56.730121Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}