Pasteurella multocida Toxin as a Transporter of Non-Cell-Permeating Proteins
العنوان: | Pasteurella multocida Toxin as a Transporter of Non-Cell-Permeating Proteins |
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المؤلفون: | Joachim H. C. Orth, Doris Jehle, Carsten Schwan, Stefan Bergmann, Klaus Aktories |
المصدر: | Infection and Immunity. 81:2459-2467 |
بيانات النشر: | American Society for Microbiology, 2013. |
سنة النشر: | 2013 |
مصطلحات موضوعية: | Cell Membrane Permeability, Cell Survival, G protein, Recombinant Fusion Proteins, Bacterial Toxins, Immunology, Golgi Apparatus, Endosomes, Biology, medicine.disease_cause, Microbiology, Cytosol, Bacterial Proteins, Cell surface receptor, Heterotrimeric G protein, medicine, Humans, Diphtheria Toxin, Cloning, Molecular, Diphtheria toxin, Cellular Microbiology: Pathogen-Host Cell Molecular Interactions, Toxin, Fusion protein, Molecular biology, Peptide Fragments, Protein Structure, Tertiary, Transport protein, Elongation factor, Protein Transport, HEK293 Cells, Infectious Diseases, Parasitology, Macrolides, Caco-2 Cells, Biomarkers, Protein Binding |
الوصف: | The protein toxin Pasteurella multocida toxin (PMT) is the causative agent of atrophic rhinitis in pigs, leading to atrophy of the nasal turbinate bones by affecting osteoblasts and osteoclasts. The mechanism of PMT-induced intoxication is a deamidation of α-subunits of heterotrimeric G proteins, including Gα q , Gα 13 , and Gα i , thereby causing persistent activation of the G proteins. Here we utilized PMT as a transporter of the non-cell-permeating A domain of diphtheria toxin (DTa). Fusion proteins of PMT and DTa ADP-ribosylated elongation factor 2, the natural target of diphtheria toxin, leading to cell toxicity. PMT-DTa effects were competed by PMT, indicating binding to the same cell surface receptor. Fluorescently labeled PMT-DTa and PMT colocalized with specific markers of early and late endosomes. Bafilomycin A, which inhibits vacuolar H + -ATPase, blocked PMT-DTa-induced intoxication of HEK-293 cells. By constructing various PMT-DTa chimeras, we identified a minimal region of PMT necessary for uptake of DTa. The data suggest that PMT is able to transport cargo proteins into eukaryotic cells by utilizing the PMT-specific uptake route. |
تدمد: | 1098-5522 0019-9567 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8a059a6409efe4f6ef6a6d549e8c149d https://doi.org/10.1128/iai.00429-13 |
حقوق: | OPEN |
رقم الأكسشن: | edsair.doi.dedup.....8a059a6409efe4f6ef6a6d549e8c149d |
قاعدة البيانات: | OpenAIRE |
تدمد: | 10985522 00199567 |
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