{"doi":"10.1073/pnas.2203272119","title":"Structures of a large prolate virus capsid in unexpanded and expanded states generate insights into the icosahedral virus assembly","abstract":"<jats:p>Many icosahedral viruses assemble proteinaceous precursors called proheads or procapsids. Proheads are metastable structures that undergo a profound structural transition known as expansion that transforms an immature unexpanded head into a mature genome-packaging head. Bacteriophage T4 is a model virus, well studied genetically and biochemically, but its structure determination has been challenging because of its large size and unusually prolate-shaped, ∼1,200-Å-long and ∼860-Å-wide capsid. Here, we report the cryogenic electron microscopy (cryo-EM) structures of T4 capsid in both of its major conformational states: unexpanded at a resolution of 5.1 Å and expanded at a resolution of 3.4 Å. These are among the largest structures deposited in Protein Data Bank to date and provide insights into virus assembly, head length determination, and shell expansion. First, the structures illustrate major domain movements and ∼70% additional gain in inner capsid volume, an essential transformation to contain the entire viral genome. Second, intricate intracapsomer interactions involving a unique insertion domain dramatically change, allowing the capsid subunits to rotate and twist while the capsomers remain fastened at quasi-threefold axes. Third, high-affinity binding sites emerge for a capsid decoration protein that clamps adjacent capsomers, imparting extraordinary structural stability. Fourth, subtle conformational changes at capsomers’ periphery modulate intercapsomer angles between capsomer planes that control capsid length. Finally, conformational changes were observed at the symmetry-mismatched portal vertex, which might be involved in triggering head expansion. These analyses illustrate how small changes in local capsid subunit interactions lead to profound shifts in viral capsid morphology, stability, and volume.</jats:p>","journal":"Proceedings of the National Academy of Sciences","year":2022,"id":17076,"datarank":1.0224524714073957,"base_score":3.4657359027997265,"endowment":3.4657359027997265,"self_citation_contribution":0.519860385419959,"citation_network_contribution":0.5025920859874368,"self_endowment_contribution":0.519860385419959,"citer_contribution":0.5025920859874368,"corpus_percentile":null,"corpus_rank":null,"citation_count":31,"citer_count":21,"citers_with_citation_signal":17,"citers_with_endowment":17,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":123455,"name":"Wei-Chun Tang","orcid":null,"position":1,"is_corresponding":false},{"id":123456,"name":"Andrei Fokine","orcid":"0000-0001-9349-1619","position":2,"is_corresponding":false},{"id":123457,"name":"Marthandan Mahalingam","orcid":null,"position":3,"is_corresponding":false},{"id":123458,"name":"Qianqian Shao","orcid":"0000-0001-9937-0631","position":4,"is_corresponding":false},{"id":91658,"name":"Michael G. Rossmann","orcid":"0000-0002-9468-9309","position":5,"is_corresponding":false},{"id":123459,"name":"Venigalla B. Rao","orcid":"0000-0002-0777-6587","position":6,"is_corresponding":false},{"id":123454,"name":"Qianglin Fang","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":3.4657359027997265,"endowment":3.4657359027997265,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"36161892","pmcid":"PMC9546572","openalex_id":"https://openalex.org/W4297093734","authors":[],"funders":[{"funder_name":"HHS | National Institutes of Health","grant_id":"AI081726","title":null},{"funder_name":"National Science Foundation","grant_id":"MCB-0923873","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R01 AI081726","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R56 AI081726","title":null},{"funder_name":"National Science Foundation","grant_id":"0923873","title":"Mechanism of ATP-driven DNA Packaging in Bacteriophage T4"},{"funder_name":"National Institutes of Health","grant_id":"2R01AI081726-06A1","title":"Structural studies of bacteriophage T4 and their potential medical applications"}],"total_grants":6,"fwci":4.7435,"citation_percentile":0.95195081,"influential_citations":1,"citation_trend":[{"year":2022,"count":1},{"year":2023,"count":11},{"year":2024,"count":7},{"year":2025,"count":9},{"year":2026,"count":3}],"oa_status":"green","license":"cc-by-nc-nd","oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/9546572","host_type":"repository"},{"url":"https://doi.org/10.1073/pnas.2203272119","host_type":"HYBRID"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/9546572","host_type":"repository"},{"url":"https://pnas.org/doi/pdf/10.1073/pnas.2203272119","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/36161892","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC9546572","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC9546572?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.1073/pnas.2203272119","host_type":""}],"fields_of_study":["Bacteriophages and microbial interactions","Animal Virus Infections Studies","Viral gastroenteritis research and epidemiology","Medicine","Biology","Materials Science","Physics","0301 basic medicine","0303 health sciences","03 medical and health sciences","Bacteriophage T4","Capsid","Capsid Proteins","Cryoelectron Microscopy","Protein Domains","Virion","Virus Assembly"],"mesh_terms":["Protein Domains","Capsid","Virion","Bacteriophage T4","Virus Assembly","Cryoelectron Microscopy","Capsid Proteins"],"keywords":["Icosahedral symmetry","Capsid","Prolate spheroid","Capsomere","Virology","Virus","Physics","Biology","Chemistry","Crystallography","Classical mechanics","virus assembly","Bacteriophage T4","Capsid Expansion","Capsid Length Control","Prolate Virus Structure","Protein Domains","Cryoelectron Microscopy","Virion","Capsid Proteins","Biological Sciences"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. Good health"},{"sdg_number":0,"sdg_label":"Life in Land"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"pdb"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-02T16:34:59.814617Z","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":[]}