National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
R01AI068041-14
米国
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
R01AI108834-07
米国
Howard Hughes Medical Institute (HHMI)
米国
引用
ジャーナル: Science / 年: 2024 タイトル: Native architecture of a human GBP1 defense complex for cell-autonomous immunity to infection. 著者: Shiwei Zhu / Clinton J Bradfield / Agnieszka Maminska / Eui-Soon Park / Bae-Hoon Kim / Pradeep Kumar / Shuai Huang / Minjeong Kim / Yongdeng Zhang / Joerg Bewersdorf / John D MacMicking / 要旨: 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 ...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.