Structural Basis of Cytotoxicity Mediated by the Type III Secretion Toxin ExoU from Pseudomonas aeruginosa

• DOI: 10.1371/journal.ppat.1002637
• Publication Date: 2012-04-05T20:53:48Z
• Authors: Claire Gendrin; Carlos Contreras-...; Stéphanie Bouillot; Sylvie Elsen; David Lemaire; Dimitrios A. Skou...; Philippe Huber; Ina Attree; Andréa Dessen
• Keywords: Phosphatidylinositol 4,5-Diphosphate; 0301 basic medicine; 570; Protein Folding; QH301-705.5; [SDV]Life Sciences [q-bio]; Bacterial Toxins; Eukaryotic cells; Structure-Activity Relationship; 03 medical and health sciences; Secretion systems; Bacterial Proteins; Toxins; Humans; Pseudomonas Infections; Biology (General); Bacterial Secretion Systems; Membrane potential; Ubiquitination; 500; RC581-607; Protein Structure, Tertiary; 3. Good health; Cell membranes; [SDV] Life Sciences [q-bio]; Phospholipases; Pseudomonas aeruginosa; Immunologic diseases. Allergy; Research Article; HeLa Cells; Molecular Chaperones

The type III secretion system (T3SS) is a complex macromolecular machinery employed by number of Gram-negative pathogens to inject effectors directly into the cytoplasm eukaryotic cells. ExoU from opportunistic pathogen Pseudomonas aeruginosa one most aggressive toxins injected T3SS, leading rapid cell necrosis. Here we report crystal structure in with its chaperone, SpcU. folds membrane-binding, bridging, and phospholipase domains. SpcU maintains N-terminus an unfolded state, required for secretion. domain carries embedded catalytic site whose position within does not permit direct interaction bilayer, which suggests that must undergo conformational rearrangement order access lipids target membrane. bridging connects membrane-binding domains, latter displays specificity PI(4,5)P2. Both transfection experiments infection cells ExoU-secreting bacteria show ubiquitination results co-localization endosomal markers. This could reflect attempt infected degradation protect itself cytotoxic action.