Native 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 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:383 |
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| Enthalten in: |
Science (New York, N.Y.) - 383(2024), 6686 vom: 05. März, Seite eabm9903 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhu, Shiwei [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 04.03.2024 Date Revised 04.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1126/science.abm9903 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a 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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| 700 | 1 | |a Bradfield, Clinton J |e verfasserin |4 aut | |
| 700 | 1 | |a Maminska, Agnieszka |e verfasserin |4 aut | |
| 700 | 1 | |a Park, Eui-Soon |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Bae-Hoon |e verfasserin |4 aut | |
| 700 | 1 | |a Kumar, Pradeep |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Shuai |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Minjeong |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yongdeng |e verfasserin |4 aut | |
| 700 | 1 | |a Bewersdorf, Joerg |e verfasserin |4 aut | |
| 700 | 1 | |a MacMicking, John D |e verfasserin |4 aut | |
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