title: Characterization of lipid binding specificities of dysferlin C2 domains reveals novel interactions with phosphoinositides.
abstract: Dysferlin is a type II transmembrane protein implicated in Ca(2+)-dependent sarcolemmal membrane repair. Dysferlin has seven C2 domains, which are lipid and protein binding modules. In this study, we sought to characterize the lipid binding specificity of dysferlin's seven C2 domains. Dysferlin's C2A domain was able to bind to phosphatidylserine (PS), phosphatidylinositol 4-phosphate [PtdIns(4)P], and phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P(2)] in a Ca(2+)-dependent fashion. The remainder of the C2 domains exhibited weaker and Ca(2+)-independent binding to PS and no significant binding to phosphoinositides.
authors.affiliation: Neuromuscular Research Group, Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada.
authors.forename: Christian
authors.initials: C
authors.lastname: Therrien
authors.forename: Sabrina
authors.initials: S
authors.lastname: Di Fulvio
authors.forename: Sarah
authors.initials: S
authors.lastname: Pickles
authors.forename: Michael
authors.initials: M
authors.lastname: Sinnreich
mesh_terms: D000595:Amino Acid Sequence; D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D000073939:Dysferlin; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D010716:Phosphatidylinositols / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment
chemical_list: C114839:DYSF protein, human; D000073939:Dysferlin; D008565:Membrane Proteins; D009124:Muscle Proteins; D010716:Phosphatidylinositols; D002118:Calcium