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TitleA human apolipoprotein L with detergent-like activity kills intracellular pathogens.
Journal, issue, pagesScience, Vol. 373, Issue 6552, Year 2021
Publish dateJul 16, 2021
AuthorsRyan 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 /
PubMed AbstractActivation 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.
External linksScience / PubMed:34437126 / PubMed Central
MethodsEM (single particle)
Resolution15.0 Å
Structure data

EMDB-24144:
ApoL3, A human apolipoprotein L
Method: EM (single particle) / Resolution: 15.0 Å

Source
  • Homo sapiens (human)

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