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6 février 2020: 1 événement

  • Département Biochimie, Biophysique et Biologie Structurale

    Jeudi 6 février 14:00-17:30 - Thibaud Dieudonné - Laboratoire des Protéines et Systèmes Membranaires, I2BC

    Functional and structural characterization of lipid flippases : the yeast Drs2p/Cdc50p and the disease-related human ATP8B1/CDC50A complexes

    Résumé : Living cells are surrounded by membranes organized in bilayers, separating the intracellular medium from the extracellular environment. A hallmark of eukaryotic membranes from the late secretory/endocytic pathways is the asymmetric distribution of phospholipids between the two leaflets. Indeed, phosphatidylcholine (PC) and sphingolipids (SL) are mainly found in the outer leaflet whereas phosphatidylserine (PS) and phosphatidylethanolamine (PE) are sequestered in the inner leaflet. This asymmetry is maintained thanks to different membrane lipid transporters. Among them, flippases, which are transporters fueled by ATP hydrolysis, translocate lipids from the outer to the inner leaflet. Flippases belong to the P4-ATPase family and have been linked to several diseases. For instance, mutated forms of a human P4-ATPase, ATP8B1, are responsible for intrahepatic cholestasis, a severe liver disease. In this thesis, we investigated the regulatory mechanism of two flippases, the yeast PS-specific flippase complex Drs2p/Cdc50p, and the human disease-related flippase complex ATP8B1/CDC50A. Both proteins were expressed in S. cerevisiae and purified for downstream functional characterization. Our results demonstrate that both flippases are tightly regulated by phosphoinositides and autoinhibited by their N- and C-terminal extensions.

    Lieu : Auditorium I2BC - Bâtiment 21, Campus de GIf-sur-Yvette

    En savoir plus : Département Biochimie, Biophysique et Biologie Structurale