TY - JOUR TI - Guanylate binding proteins directly attack Toxoplasma gondii via supramolecular complexes AU - Kravets, Elisabeth AU - Degrandi, Daniel AU - Ma, Qijun AU - Peulen, Thomas-Otavio AU - Klümpers, Verena AU - Felekyan, Suren AU - Kühnemuth, Ralf AU - Weidtkamp-Peters, Stefanie AU - Seidel, Claus AM AU - Pfeffer, Klaus A2 - Ha, Taekjip VL - 5 PY - 2016 DA - 2016/01/27 SP - e11479 C1 - eLife 2016;5:e11479 DO - 10.7554/eLife.11479 UR - https://doi.org/10.7554/eLife.11479 AB - GBPs are essential for immunity against intracellular pathogens, especially for Toxoplasma 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. KW - host-pathogen interaction KW - cell-autonomous immunity KW - guanylate-binding proteins KW - Förster resonance energy transfer KW - multiparameter fluorescence image spectroscopy JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -