title: Binding of the dystrophin second repeat to membrane di-oleyl phospholipids is dependent upon lipid packing.
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.
authors.affiliation: UMR CNRS 6026 - IFR 140, Equipe RMN-Interactions lipides protéines, Faculté de Médecine, Université de Rennes 1, CS 34317, 35043 Rennes cedex, France. elisabeth.lerumeur@univ-rennes1.fr
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Le Rumeur
authors.forename: Sandrine
authors.initials: S
authors.lastname: Pottier
authors.forename: Gregory
authors.initials: G
authors.lastname: Da Costa
authors.forename: Laurent
authors.initials: L
authors.lastname: Metzinger
authors.forename: Liza
authors.initials: L
authors.lastname: Mouret
authors.forename: Chantal
authors.initials: C
authors.lastname: Rocher
authors.forename: Marie
authors.initials: M
authors.lastname: Fourage
authors.forename: Corinne
authors.initials: C
authors.lastname: Rondeau-Mouro
authors.forename: Arnaud
authors.initials: A
authors.lastname: Bondon
mesh_terms: D016189:Dystrophin / Q000737:chemistry / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008027:Light; D008563:Membrane Lipids / Q000737:chemistry*; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism*; D020449:Repetitive Sequences, Amino Acid; D012542:Scattering, Radiation; D055672:Static Electricity; D053835:Unilamellar Liposomes / Q000737:chemistry
chemical_list: D016189:Dystrophin; D008563:Membrane Lipids; D010743:Phospholipids; D053835:Unilamellar Liposomes