Structure of an Apolipoprotein-Phospholipid Complex: ApoC-III Induced Changes in the Physical Properties of Dimyristoylphosphatidylcholine

The effect of ApoC-III, a major apoprotein constituent of human very low density lipoproteins, on the physical properties of dimyristoylphosphatidylcholine (DMPC) vesicles has been studied by magnetic resonance and fluorescence techniques. The sharp gel ⟶ liquid crystalline transition usually observed at 23 °C in DMPC is both broadened and elevated when ApoC-III is bound as determined (a) from measurements of microscopic viscosity by pyrene excimer fluorescence, (b) from the distribution of di-tert-butyl nitroxide between the bulk aqueous phase and the fluid lipid phase, and (c) from the motion of fatty acyl chains of spinlabeled phosphatidylcholine. Experiments involving the translocation of ascorbate and charged nitroxide ions and the movement of paramagnetic Eu³⁺ ions indicate that when ApoC-III binds to DMPC vesicles, it increases their permeability or destroys their original bilayer structure. These two possibilities were distinguishable by gel filtration of the DMPC-ApoC-III complex (~34 mol/mol) that indicated that the product particles were significantly smaller than the original vesicles. Taken together, the data indicate that ApoC-III binding to DMPC not only decreases the acyl chain motion of individual lipid molecules, but also induces breakdown of bilamellar vesicular structure to give significantly smaller complexes.