Cryo-ET of a human GBP coatomer governing cell-autonomous innate immunity to infection
Abstract All living organisms deploy cell-autonomous defenses to combat infection. In plants and animals, these activities generate large supramolecular complexes that recruit immune proteins for protection. Here, we solve the native structure of a massive antimicrobial complex generated by polymerization of 30,000 human guanylate-binding proteins (GBPs) over the entire surface of virulent bacteria. Construction of this giant nanomachine takes ∼1-3 minutes, remains stable for hours, and acts as a cytokine and cell death signaling platform atop the coated bacterium. Cryo-ET of this “coatomer” revealed thousands of human GBP1 molecules undergo ∼260 Å insertion into the bacterial outer membrane, triggering lipopolysaccharide release that activates co-assembled caspase-4. Together, our results provide a quasi-atomic view of how the GBP coatomer mobilizes cytosolic immunity to combat infection in humans.One-Sentence Summary Thousands of GBPs coat cytosolic bacteria to engineer an antimicrobial signaling platform inside human cells..
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Preprint| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
bioRxiv.org - (2021) vom: 30. Aug. Zur Gesamtaufnahme - year:2021 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhu, Shiwei [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.1101/2021.08.26.457804 |
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| PPN (Katalog-ID): |
XBI03246925X |
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| 100 | 1 | |a Zhu, Shiwei |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Cryo-ET of a human GBP coatomer governing cell-autonomous innate immunity to infection |
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| 520 | |a Abstract All living organisms deploy cell-autonomous defenses to combat infection. In plants and animals, these activities generate large supramolecular complexes that recruit immune proteins for protection. Here, we solve the native structure of a massive antimicrobial complex generated by polymerization of 30,000 human guanylate-binding proteins (GBPs) over the entire surface of virulent bacteria. Construction of this giant nanomachine takes ∼1-3 minutes, remains stable for hours, and acts as a cytokine and cell death signaling platform atop the coated bacterium. Cryo-ET of this “coatomer” revealed thousands of human GBP1 molecules undergo ∼260 Å insertion into the bacterial outer membrane, triggering lipopolysaccharide release that activates co-assembled caspase-4. Together, our results provide a quasi-atomic view of how the GBP coatomer mobilizes cytosolic immunity to combat infection in humans.One-Sentence Summary Thousands of GBPs coat cytosolic bacteria to engineer an antimicrobial signaling platform inside human cells. | ||
| 700 | 1 | |a Bradfield, Clinton J. |e verfasserin |4 aut | |
| 700 | 1 | |a Mamińska, 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 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 | |
| 773 | 0 | 8 | |i Enthalten in |t bioRxiv.org |g (2021) vom: 30. Aug. |
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