A human apolipoprotein L with detergent-like activity kills intracellular pathogens
Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works..
Activation of cell-autonomous defense by the immune cytokine interferon-γ (IFN-γ) is critical to the control of life-threatening infections in humans. IFN-γ induces the expression of hundreds of host proteins in all nucleated cells and tissues, yet many of these proteins remain uncharacterized. We screened 19,050 human genes by CRISPR-Cas9 mutagenesis and identified IFN-γ-induced apolipoprotein L3 (APOL3) as a potent bactericidal agent protecting multiple non-immune barrier cell types against infection. Canonical apolipoproteins typically solubilize mammalian lipids for extracellular transport; APOL3 instead targeted cytosol-invasive bacteria to dissolve their anionic membranes into human-bacterial lipoprotein nanodiscs detected by native mass spectrometry and visualized by single-particle cryo-electron microscopy. Thus, humans have harnessed the detergent-like properties of extracellular apolipoproteins to fashion an intracellular lysin, thereby endowing resident nonimmune cells with a mechanism to achieve sterilizing immunity.
| Errataetall: |
CommentIn: Science. 2021 Jul 16;373(6552):276-277. - PMID 34437138 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:373 |
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| Enthalten in: |
Science (New York, N.Y.) - 373(2021), 6552 vom: 16. Juli |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Gaudet, Ryan G [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 17.09.2021 Date Revised 13.12.2023 published: Print CommentIn: Science. 2021 Jul 16;373(6552):276-277. - PMID 34437138 Citation Status MEDLINE |
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| doi: |
10.1126/science.abf8113 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM329802429 |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. | ||
| 520 | |a Activation of cell-autonomous defense by the immune cytokine interferon-γ (IFN-γ) is critical to the control of life-threatening infections in humans. IFN-γ induces the expression of hundreds of host proteins in all nucleated cells and tissues, yet many of these proteins remain uncharacterized. We screened 19,050 human genes by CRISPR-Cas9 mutagenesis and identified IFN-γ-induced apolipoprotein L3 (APOL3) as a potent bactericidal agent protecting multiple non-immune barrier cell types against infection. Canonical apolipoproteins typically solubilize mammalian lipids for extracellular transport; APOL3 instead targeted cytosol-invasive bacteria to dissolve their anionic membranes into human-bacterial lipoprotein nanodiscs detected by native mass spectrometry and visualized by single-particle cryo-electron microscopy. Thus, humans have harnessed the detergent-like properties of extracellular apolipoproteins to fashion an intracellular lysin, thereby endowing resident nonimmune cells with a mechanism to achieve sterilizing immunity | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Zhu, Shiwei |e verfasserin |4 aut | |
| 700 | 1 | |a Halder, Anushka |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Bae-Hoon |e verfasserin |4 aut | |
| 700 | 1 | |a Bradfield, Clinton J |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Shuai |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Dijin |e verfasserin |4 aut | |
| 700 | 1 | |a Mamiñska, Agnieszka |e verfasserin |4 aut | |
| 700 | 1 | |a Nguyen, Thanh Ngoc |e verfasserin |4 aut | |
| 700 | 1 | |a Lazarou, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Karatekin, Erdem |e verfasserin |4 aut | |
| 700 | 1 | |a Gupta, Kallol |e verfasserin |4 aut | |
| 700 | 1 | |a MacMicking, John D |e verfasserin |4 aut | |
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