Binding of the dystrophin second repeat to membrane di-oleyl phospholipids is dependent upon lipid packing |
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Authors: | Elisabeth Le Rumeur Sandrine Pottier Laurent Metzinger Chantal Rocher Corinne Rondeau-Mouro |
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Institution: | a UMR CNRS 6026 - IFR 140, Equipe RMN-Interactions lipides protéines, Faculté de Médecine, Université de Rennes 1, CS 34317, 35043 Rennes cedex, France b UPRES JE 2311 - IFR 140, Faculté de Pharmacie, Université de Rennes 1, CS 34317, 35043 Rennes cedex, France c Unité BIA-INRA, Plateforme RIO-Biopolymères, Interactions et Biologie Structurale, Rue de la Géraudière, BP 71627, 44316 Nantes cedex 3, France |
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Abstract: | Dystrophin is the genetically deficient protein in Duchenne Muscular Dystrophy. Its C- and N-terminal ends interact with cytoskeletal and membrane proteins, establishing a link between the cytoskeleton and the extracellular matrix. In a previous study, we showed that there is an interaction between the second repeat of the rod domain and membrane phospholipids, which places tryptophan residues in close contact with the membrane. Here, we examine the binding of the dystrophin repeat-2 to small unilamellar vesicles with varying composition. We find that the protein binds predominantly to di-oleyl-phosphatidylserine. The binding as a function of increasing mol% of DOPS appears to be cooperative due to reduction of dimensionality, greatly enhanced in the absence of salts, and partly modulated by pH. Substituting small by large unilamellar vesicles induces a 30-fold lower affinity of the protein for the membrane phospholipids. However, modifying the packing of the acyl chains by introducing lipids such as phosphatidylethanolamine and cholesterol to the vesicle leads to an approximately 7-fold increase in affinity. Taken together, these results show that the binding involves electrostatic forces in addition to hydrophobic ones. |
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Keywords: | DOPC dioleyl-phosphatidylcholine DOPS dioleyl-phosphatidylserine DOPG dioleyl-phosphatidylglycerol DOPA dioleyl-phosphatidic acid DOPE dioleyl-phosphatidylethanolamine SUVs small unilamellar vesicles LUVs large unilamellar vesicles DYSR2 repeat 2 of dystrophin rod domain |
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