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Mécanismes Moléculaires impliqués dans les Myopathies: Analyses des interactions Dystrophine-Lipides.

Joe Sarkis 1 
1 RMN et Interactions Lipides-Protéines
ICM - Interactions cellulaires et moléculaires, IPR - Institut de Physique de Rennes
Abstract : The characterization of the interactions of different biomolecules such as proteins and peptides with lipids, constitute a crucial step for better understanding the behavior and mechanisms of action of such molecules with cell membranes. We present here biomimetic studies of a muscular protein by using different membrane models and biophysical methods. Dystrophin is a long filamentous protein essential to skeletal muscle function. Its deficiency or mutated forms are responsible of muscular dystrophies. In the present study, we analyzed the properties of different spectrin like repeats from the dystrophin central domain. We characterized the specific interactions of two different subdomains constituted by the repeats 1 to 3 and 20 to 24 with lipids. We further show that the interaction and the organization of the repeats 11 to 15 with both anionic and zwitterionic membranes are modulated by lipid curvature as well as by lipid packing. Surface rheology measurements show that repeats 11 to 15 constitute a functional link between the membrane and cytoskeletal actin filaments. This mechanical bridge could contribute in vivo to the shock absorber function of dystrophin during contraction-relaxation cycles in muscle cells. In the last part of this work, we studied the structure-activity relationship of a "de novo" antimicrobial peptides K4. We identify a detergent-like mechanism for the antimicrobial activity of this peptide.
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Submitted on : Monday, March 12, 2012 - 4:49:46 PM
Last modification on : Wednesday, March 30, 2022 - 2:35:56 PM
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  • HAL Id : tel-00678400, version 1


Joe Sarkis. Mécanismes Moléculaires impliqués dans les Myopathies: Analyses des interactions Dystrophine-Lipides.. Biophysique. Université Rennes 1; Université Européenne de Bretagne, 2011. Français. ⟨tel-00678400⟩



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