{"doi":"10.1101/2023.04.20.537723","title":"Structure and assembly of a bacterial gasdermin pore","abstract":"Abstract In response to pathogen infection, gasdermin (GSDM) proteins form membrane pores that induce a host cell death process called pyroptosis 1–3 . Studies of human and mouse GSDM pores reveal the functions and architectures of 24–33 protomers assemblies 4–9 , but the mechanism and evolutionary origin of membrane targeting and GSDM pore formation remain unknown. Here we determine a structure of a bacterial GSDM (bGSDM) pore and define a conserved mechanism of pore assembly. Engineering a panel of bGSDMs for site-specific proteolytic activation, we demonstrate that diverse bGSDMs form distinct pore sizes that range from smaller mammalian-like assemblies to exceptionally large pores containing >50 protomers. We determine a 3.3 Å cryo-EM structure of a Vitiosangium bGSDM in an active slinky-like oligomeric conformation and analyze bGSDM pores in a native lipid environment to create an atomic-level model of a full 52-mer bGSDM pore. Combining our structural analysis with molecular dynamics simulations and cellular assays, our results support a stepwise model of GSDM pore assembly and suggest that a covalently bound palmitoyl can leave a hydrophobic sheath and insert into the membrane before formation of the membrane-spanning β-strand regions. These results reveal the diversity of GSDM pores found in nature and explain the function of an ancient post-translational modification in enabling programmed host cell death.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":391319,"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":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9546,"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":271125,"name":"Megan L. Mayer","orcid":"0000-0001-9738-786X","position":1,"is_corresponding":false},{"id":1163629,"name":"Stefan L. Schaefer","orcid":"0000-0001-7942-8701","position":2,"is_corresponding":false},{"id":846761,"name":"Nora K. McNamara-Bordewick","orcid":"0000-0003-4747-0627","position":3,"is_corresponding":false},{"id":240042,"name":"Gerhard Hummer","orcid":"0000-0001-7768-746X","position":4,"is_corresponding":false},{"id":230272,"name":"Philip J. Kranzusch","orcid":"0000-0002-4943-733X","position":5,"is_corresponding":false},{"id":442523,"name":"Alex G. Johnson","orcid":null,"position":0,"is_corresponding":true}],"reference_count":62,"raw_metadata":null,"created_at":"2026-07-19T01:18:42.653719Z","pmid":"37131678","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":[]}