Nos tutelles


Nos partenaires


3 juillet 2017: 1 événement

  • Département Microbiologie

    Lundi 3 juillet 2017 11:30-12:30 - Dr Ekaterina Nestorovich - Biology Department The Catholic University of America, Washington DC, Etats-Unis

    Lipid dynamics and the anthrax toxin pH-dependent intracellular journey

    Résumé : Lipid microenvironment has been shown to play a critical role in the intoxication process of many bacterial exotoxins. In this study, we use planar lipid bilayer technique to gain insight into the role of the lipid dynamics in the anthrax toxin uptake. The tripartite anthrax toxin is secreted as three separate proteins, lethal factor (LF), edema factor (EF), and protective antigen (PA), that self-assemble at the cell surface to form toxic complexes. The anthrax toxin intracellular journey begins from PA binding to its cellular receptors, proteolytic cleavage to PA63, oligomerization to form heptameric/octameric prepores, and LF and EF binding followed by endocytosis. The mild acidic environment of the early endosome causes conformational changes in PA63 leading to its insertion into endosomal limiting and intraluminal vesicle (ILV) membranes and ion channel formation. The PA63-mediated delivery of LF to cytoplasm was suggested to take place later in the endocytic pathway via the back-fusion of ILVs. It is well appreciated that the lipid composition changes dramatically along the endocytic pathway with ILV membranes containing up to 70% of anionic bis(monoacylglycero)phosphate (BMP) lipid. Here we investigate if the unique stereoconfiguration of BMP contributes to the anthrax toxin properties, such as PA63 channel formation and structural dynamics as well as LF binding and translocation. Surprisingly, the channel formation was suppressed in the BMP membranes compared to PC, a phenomenon that could not be explained by the negative charge of this lipid because the channel formation was significantly enhanced when tested in PS. At the same time, LF was shown to bind about 10 and 100 times less effectively to PA63, when the channels were reconstituted into BMP and PS membranes respectively, compared with PC. The lipid dependence of the PA63/LF binding reaction was pH-dependent with PC/PS difference in IC50 nearly disappearing at pH > 6. These findings suggest that the anthrax toxin complex can be investigated and developed as a robust universal model system to study protein/lipid and protein/protein interactions as well as bilayer properties using lipid membranes of different composition.
    Invitée par l’équipe "Biologie Moléculaire des Corynébactéries et des Mycobactéries"

    Lieu : Salle de séminaires - Bâtiment 400, Campus d’Orsay

    En savoir plus : Département Microbiologie