National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
R01AI068041-14
United States
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
R01AI108834-07
United States
Howard Hughes Medical Institute (HHMI)
United States
Citation
Journal: Science / Year: 2021 Title: A human apolipoprotein L with detergent-like activity kills intracellular pathogens. Authors: Ryan G Gaudet / Shiwei Zhu / Anushka Halder / Bae-Hoon Kim / Clinton J Bradfield / Shuai Huang / Dijin Xu / Agnieszka Mamiñska / Thanh Ngoc Nguyen / Michael Lazarou / Erdem Karatekin / ...Authors: Ryan G Gaudet / Shiwei Zhu / Anushka Halder / Bae-Hoon Kim / Clinton J Bradfield / Shuai Huang / Dijin Xu / Agnieszka Mamiñska / Thanh Ngoc Nguyen / Michael Lazarou / Erdem Karatekin / Kallol Gupta / John D MacMicking / Abstract: 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 ...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.
History
Deposition
Jun 1, 2021
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Header (metadata) release
Sep 15, 2021
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Map release
Sep 15, 2021
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Update
Sep 15, 2021
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Current status
Sep 15, 2021
Processing site: RCSB / Status: Released
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