先天免疫系统
免疫
细胞生物学
生物
脂多糖
半胱氨酸蛋白酶
微生物学
免疫学
免疫系统
程序性细胞死亡
细胞凋亡
生物化学
作者
Shiwei Zhu,Clinton J. Bradfield,Agnieszka Mamińska,Eui‐Soon Park,Bae-Hoon Kim,Pradeep Kumar,Shuai Huang,Minjeong Kim,Yongdeng Zhang,Joerg Bewersdorf,John D. MacMicking
出处
期刊:Science
[American Association for the Advancement of Science (AAAS)]
日期:2024-02-29
卷期号:383 (6686)
被引量:5
标识
DOI:10.1126/science.abm9903
摘要
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.
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