title: Spectrin-like repeats 11-15 of human dystrophin show adaptations to a lipidic environment.
abstract: Dystrophin is essential to skeletal muscle function and confers resistance to the sarcolemma by interacting with cytoskeleton and membrane. In the present work, we characterized the behavior of dystrophin 11-15 (DYS R11-15), five spectrin-like repeats from the central domain of human dystrophin, with lipids. DYS R11-15 displays an amphiphilic character at the liquid/air interface while maintaining its secondary α-helical structure. The interaction of DYS R11-15 with small unilamellar vesicles (SUVs) depends on the lipid nature, which is not the case with large unilamellar vesicles (LUVs). In addition, switching from anionic SUVs to anionic LUVs suggests the lipid packing as a crucial factor for the interaction of protein and lipid. The monolayer model and the modulation of surface pressure aim to mimic the muscle at work (i.e. dynamic changes of muscle membrane during contraction and relaxation) (high and low surface pressure). Strikingly, the lateral pressure modifies the protein organization. Increasing the lateral pressure leads the proteins to be organized in a regular network. Nevertheless, a different protein conformation after its binding to monolayer is revealed by trypsin proteolysis. Label-free quantification by nano-LC/MS/MS allowed identification of the helices in repeats 12 and 13 involved in the interaction with anionic SUVs. These results, combined with our previous studies, indicate that DYS R11-15 constitutes the only part of dystrophin that interacts with anionic as well as zwitterionic lipids and adapts its interaction and organization depending on lipid packing and lipid nature. We provide strong experimental evidence for a physiological role of the central domain of dystrophin in sarcolemma scaffolding through modulation of lipid-protein interactions.
authors.affiliation: Université Européenne de Bretagne, 35000 Rennes, France; UMR-CNRS 6026-IFR 140, Equipe RMN-Interactions Lipides Protéines, Faculté de Médecine, CS 34317, 35043 Rennes, France; UMR-CNRS 6251, Institut de Physique de Rennes, Université de Rennes 1, 35042 Rennes, France.
authors.forename: Joe
authors.initials: J
authors.lastname: Sarkis
authors.affiliation: Université Européenne de Bretagne, 35000 Rennes, France; UMR-CNRS 6026-IFR 140, Equipe RMN-Interactions Lipides Protéines, Faculté de Médecine, CS 34317, 35043 Rennes, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Hubert
authors.affiliation: Université Européenne de Bretagne, 35000 Rennes, France; UMR-CNRS 6026-IFR 140, Equipe RMN-Interactions Lipides Protéines, Faculté de Médecine, CS 34317, 35043 Rennes, France.
authors.forename: Baptiste
authors.initials: B
authors.lastname: Legrand
authors.affiliation: Université Européenne de Bretagne, 35000 Rennes, France; UMR-CNRS 6251, Institut de Physique de Rennes, Université de Rennes 1, 35042 Rennes, France.
authors.forename: Estelle
authors.initials: E
authors.lastname: Robert
authors.affiliation: Université Européenne de Bretagne, 35000 Rennes, France; UMR-CNRS 6026-IFR 140, Equipe RMN-Interactions Lipides Protéines, Faculté de Médecine, CS 34317, 35043 Rennes, France.
authors.forename: Angélique
authors.initials: A
authors.lastname: Chéron
authors.affiliation: Université Européenne de Bretagne, 35000 Rennes, France; Institut National de la Recherche Agronomique (INRA), AGROCAMPUS-OUEST, UMR 1253, Science et Technologie du Lait et de l'Oeuf, 35042 Rennes, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Jardin
authors.affiliation: Université Européenne de Bretagne, 35000 Rennes, France; Laboratoire Traitement du Signal et de l'Image (LTSI), INSERM 642, 35042 Rennes, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Hitti
authors.affiliation: Université Européenne de Bretagne, 35000 Rennes, France; UMR-CNRS 6026-IFR 140, Equipe RMN-Interactions Lipides Protéines, Faculté de Médecine, CS 34317, 35043 Rennes, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Le Rumeur
authors.affiliation: Université Européenne de Bretagne, 35000 Rennes, France; UMR-CNRS 6251, Institut de Physique de Rennes, Université de Rennes 1, 35042 Rennes, France. Electronic address: veronique.vie@univ-rennes1.fr.
authors.forename: Véronique
authors.initials: V
authors.lastname: Vié
mesh_terms: D016189:Dystrophin / Q000737:chemistry / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry; D018625:Microscopy, Atomic Force / Q000379:methods; D008958:Models, Molecular; D008968:Molecular Conformation; D010743:Phospholipids / Q000737:chemistry; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013049:Spectrin / Q000737:chemistry*; D013499:Surface Properties; D014357:Trypsin / Q000737:chemistry
chemical_list: D016189:Dystrophin; D008055:Lipids; D008081:Liposomes; D010743:Phospholipids; D013049:Spectrin; D014357:Trypsin