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.
Article and author information
Author details
Reviewing Editor
- Taekjip Ha, Johns Hopkins University School of Medicine, United States
Version history
- Received: September 9, 2015
- Accepted: January 26, 2016
- Accepted Manuscript published: January 27, 2016 (version 1)
- Version of Record published: February 29, 2016 (version 2)
Copyright
© 2016, Kravets et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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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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