Cholesterol favors the anchorage of human dystrophin repeats 16 to 21 in membrane at physiological surface pressure.

Sarah Ameziane-Le Hir (1) , Céline Raguénès-Nicol (2) , Gilles Paboeuf (3) , Aurélie Nicolas (2) , Elisabeth Le Rumeur (2) , Véronique Vié (3)

1 Structures et interactions moléculaires
2 Structures et interactions moléculaires
3 IPR - Institut de Physique de Rennes

Dystrophin (DYS) is a filamentous protein that connects the cytoskeleton and the extracellular matrix via the sarcolemma, conferring resistance to muscular cells. In this study, interactions between the DYS R16-21 fragment and lipids were examined using Langmuir films made of anionic and zwitterionic lipids. The film fluidity was modified by the addition of 15% cholesterol. Whatever the lipid mixture examined, at low surface pressure (20mN/m) few differences appeared on the protein insertion and the presence of cholesterol did not affect the protein/lipid interactions. At high surface pressure (30mN/m), the protein insertion was very low and occurred only in zwitterionic films in the liquid-expanded phase. In anionic films, electrostatic interactions prevented the protein insertion outright, and caused accumulation of the protein on the hydrophilic part of the monolayer. Addition of cholesterol to both lipid mixtures drastically modified the protein-lipid interactions: the DYS R16-21 insertion increased and its organization in the monolayer appeared to be more homogeneous. The presence of accessible cholesterol recognition amino-acid consensus sequences in this fragment may enhance the protein/membrane binding at physiological lateral pressure. These results suggest that the anchorage of dystrophin to the membrane in vivo may be stabilized by cholesterol-rich nano-domains in the inner leaflet of sarcolemma.

Mots clés: Atomic force microscopy; Langmuir film; Muscular dystrophy; Protein lipid interaction; CRAC sequence; Spectrin superfamily

Domaines: Biophysique; Sciences du Vivant [q-bio]; Physique [physics]

Sarah Ameziane-Le Hir, Céline Raguénès-Nicol, Gilles Paboeuf, Aurélie Nicolas, Elisabeth Le Rumeur, et al.. Cholesterol favors the anchorage of human dystrophin repeats 16 to 21 in membrane at physiological surface pressure.. Biochimica et Biophysica Acta:Biomembranes, 2014, 1838 (5), pp.1266-73. ⟨10.1016/j.bbamem.2014.01.010⟩. ⟨hal-00965782⟩