{"doi":"10.1126/science.abm9903","title":"Native architecture of a human GBP1 defense complex for cell-autonomous immunity to infection","abstract":"All living organisms deploy cell-autonomous defenses to combat infection. In plants and animals, large supramolecular complexes often activate immune proteins for protection. In this work, we resolved the native structure of a massive host-defense complex that polymerizes 30,000 guanylate-binding proteins (GBPs) over the surface of gram-negative bacteria inside human cells. Construction of this giant nanomachine took several minutes and remained stable for hours, required guanosine triphosphate hydrolysis, and recruited four GBPs plus caspase-4 and Gasdermin D as a cytokine and cell death immune signaling platform. Cryo-electron tomography suggests that GBP1 can adopt an extended conformation for bacterial membrane insertion to establish this platform, triggering lipopolysaccharide release that activated coassembled caspase-4. Our \"open conformer\" model provides a dynamic view into how the human GBP1 defense complex mobilizes innate immunity to infection.","journal":"Science","year":2024,"id":418248,"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":53,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9462,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":400350,"name":"Clinton J. Bradfield","orcid":"0000-0001-6410-3517","position":1,"is_corresponding":false},{"id":635242,"name":"Agnieszka Mamińska","orcid":"0000-0002-1300-8242","position":2,"is_corresponding":false},{"id":808170,"name":"Eui‐Soon Park","orcid":"0000-0002-1375-8027","position":3,"is_corresponding":false},{"id":635240,"name":"Bae-Hoon Kim","orcid":"0000-0001-6866-7248","position":4,"is_corresponding":false},{"id":626032,"name":"Pradeep Kumar","orcid":"0000-0002-0892-5425","position":5,"is_corresponding":false},{"id":626031,"name":"Shuai Huang","orcid":"0000-0002-8903-122X","position":6,"is_corresponding":false},{"id":1199499,"name":"Minjeong Kim","orcid":"0000-0002-0524-9281","position":7,"is_corresponding":false},{"id":259880,"name":"Yongdeng Zhang","orcid":"0000-0002-4569-8137","position":8,"is_corresponding":false},{"id":244374,"name":"Joerg Bewersdorf","orcid":"0000-0002-4085-7020","position":9,"is_corresponding":false},{"id":626033,"name":"John D. MacMicking","orcid":"0000-0002-1734-135X","position":10,"is_corresponding":false},{"id":278668,"name":"Shiwei Zhu","orcid":"0000-0003-1145-1192","position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":null,"created_at":"2026-07-19T01:57:02.483590Z","pmid":"38422126","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":[]}