title: Membrane interactions and lipid binding of casein oligomers and early aggregates.
abstract: Caseins constitute the main protein components in mammalian milk and have critical functions in calcium transport and prevention of protein aggregation. Fibrillation and aggregation of kappa-casein, a phenomenon which has only recently been detected, might be associated with malfunctions of milk secretion and amyloidosis phenomena in the mammary glands. This study employs a newly-designed chromatic biomimetic vesicle assay to investigate the occurrence and the parameters affecting membrane interactions of casein aggregates and the contribution of individual casein members to membrane binding. We show that physiological casein colloids exhibit membrane activity, as well as early globular aggregates of kappa-casein, a prominent casein isoform. Furthermore, inhibition of kappa-casein fibrillation through complexation with alphaS-casein and beta-casein, respectively, was found to go hand in hand with induction of enhanced membrane binding; these data are important in the context of casein biology since in secreted milk kappa-casein is found only in assemblies containing also alphaS-casein and beta-casein. The chromatic experiments, complemented by transmission electron microscopy analysis and fluorescence quenching assays, also revealed significantly higher affinity early spherical aggregates of k-casein to anionic phosphatidylglycerol-lipids, as compared to zwitterionic phospholipids. Overall, this study suggests that lipid interactions play important roles in maintaining the essential physiological functions of caseins in mammalian milk.
authors.affiliation: Department of Chemistry, Ben Gurion University of the Negev, Beer Sheva 84105, Israel.
authors.forename: Miri
authors.initials: M
authors.lastname: Sokolovski
authors.forename: Tania
authors.initials: T
authors.lastname: Sheynis
authors.forename: Sofiya
authors.initials: S
authors.lastname: Kolusheva
authors.forename: Raz
authors.initials: R
authors.lastname: Jelinek
mesh_terms: D000818:Animals; D002364:Caseins / Q000737:chemistry / Q000378:metabolism; D002417:Cattle; D003102:Colloids; D008563:Membrane Lipids / Q000737:chemistry / Q000378:metabolism*; D008566:Membranes / Q000737:chemistry / Q000378:metabolism; D008823:Micelles; D010743:Phospholipids / Q000737:chemistry; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism
chemical_list: D002364:Caseins; D003102:Colloids; D008563:Membrane Lipids; D008823:Micelles; D010743:Phospholipids; D020033:Protein Isoforms