Guanylate binding proteins (GBPs) directly attack T. gondii via supramolecular complexes
- Heinrich-Heine University Düsseldorf, Germany
- Heinrich-Heine-University Düsseldorf, Germany
- Heidelberg University, Germany
Abstract
GBPs are essential for immunity against intracellular pathogens, especially for T. gondii control. Here, the molecular interactions of murine GBPs (mGBP1/2/3/5/6), homo- and hetero-multimerization properties of mGBP2 and its function in parasite killing were investigated by mutational, Multiparameter Fluorescence Image Spectroscopy, and live cell microscopy methodologies. Control of T. gondii replication by mGBP2 requires GTP hydrolysis and isoprenylation thus, enabling reversible oligomerization in vesicle-like structures. mGBP2 undergoes structural transitions between monomeric, dimeric and oligomeric states visualized by quantitative FRET analysis. mGBPs reside in at least two discrete subcellular reservoirs and attack the parasitophorous vacuole membrane (PVM) as orchestrated, supramolecular complexes forming large, densely packed multimers comprising up to several thousand monomers. This dramatic mGBP enrichment results in the loss of PVM integrity, followed by a direct assault of mGBP2 upon the plasma membrane of the parasite. These discoveries provide vital dynamic and molecular perceptions into cell-autonomous immunity.
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© 2016, Kravets et al.
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Guanylate binding proteins (GBPs) directly attack T. gondii via supramolecular complexes
eLife 5:e11479.
https://doi.org/10.7554/eLife.11479
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