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    Reconstitution of Functional Integrin alpha IIb beta 3 and Its Activation in Plasma Membrane-Mimetic Lipid Environments

    Year: 2021

    Journal: Membranes, Volume 11, JUL

    Authors: Janke, Una; Mitlehner, Alexandra; Weide, Aileen; Gutmann, Theresia; Delcea, Mihaela

    Organizations: European Research Council (ERC) Starting Grant `PredicTOOL' [637877]

    Keywords: liposomes; lipids; integrin alpha IIb beta 3; reconstitution; detergents

    The study of the platelet receptor integrin alpha IIb beta 3 in a membrane-mimetic environment without interfering signalling pathways is crucial to understand protein structure and dynamics. Our understanding of this receptor and its sequential activation steps has been tremendously progressing using structural and reconstitution approaches in model membranes, such as liposomes or supported-lipid bilayers. For most alpha IIb beta 3 reconstitution approaches, saturated short-chain lipids have been used, which is not reflecting the native platelet cell membrane composition. We report here on the reconstitution of label-free full-length alpha IIb beta 3 in liposomes containing cholesterol, sphingomyelin, and unsaturated phosphatidylcholine mimicking the plasma membrane that formed supported-lipid bilayers for quartz-crystal microbalance with dissipation (QCM-D) experiments. We demonstrate the relevance of the lipid environment and its resulting physicochemical properties on integrin reconstitution efficiency and its conformational dynamics. We present here an approach to investigate alpha IIb beta 3 in a biomimetic membrane system as a useful platform do dissect disease-relevant integrin mutations and effects on ligand binding in a lipid-specific context, which might be applicable for drug screening.
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