biostudies-literatureZhu SNIDDK NIH HHSHoward Hughes Medical InstituteNIAID NIH HHSWellcome TrustNIGMS NIH HHSeabm9903https://www.ebi.ac.uk/biostudies/studies/S-EPMC12091997biostudies-literatureUnknown383(6686)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 releaseScience (New York, N.Y.)Native architecture of a human GBP1 defense complex for cell-autonomous immunity to infection.PMC12091997R01 AI108834R01 AI068041203285/B/16/ZP30 DK045735R01 GM118486MacMicking JDBradfield CJKim BHHuang SMaminska APark ESZhang YBewersdorf JKumar PKim MZhu SfalseNative architecture of a human GBP1 defense complex for cell-autonomous immunity to infection.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 release2024-01-01T00:00:00Z2024 Mar2026-06-01T06:19:47.311Z2026-04-08T09:51:27.842ZS-EPMC120919973842212610.1126/science.abm9903