Effect of Lysophosphatidyl Choline on Interaction between Phosphatidyl Choline and Activator Protein (Apolipoprotein A-I) of Lecithin: Cholesterol Acyltransferase

Abstract

The effect of lysophosphatidyl choline on interaction and formation of high density complexes between phosphatidyl choline and apolipoprotein A-I (apoA-I), the major protein of high density lipoprotein and activator of lecithin: cholesterol acyltransferase, was investigated. Under the experimental conditions used, there was minimal high density complex formation whcn apoA-I was incubated with sonicated dispersions of phosphatidyl choline containing no lysophosphatidyl choline. Incubation of apoA-I with cosonicates of phosphatidyl choline containing 25 and 50 mole % lysophosphatidyl choline resulted in marked interaction with formation of high density (d 1.063–1.21 g/ml) lipid-protein complexes. The above complexes were predominately discoidal particles which either stacked in rouleaux or remained flat in packed arrays when observed under electron microscopy with negative staining. Discoidal complexes isolated from the incubation mixture of apoA-I plus cosonicate of phosphatidyl choline containing 25 mole % lysophosphatidyl choline were highly homogeneous with diameters in the range of 80–105 A and 40 A thickness. Incubation of apoA-I with cosonicates of phosphatidyl choline containing 75 mole % lysophosphatidyl choline produced spherical complexes 60–90 Å in diameter. The present work indicates that the effect of incorporation of lysophosphatidyl choline on the properties of high density complexes containing apoA-I and phosphatidyl choline is considerably different from that of incorporation of corresponding amounts of cholesteryl esters, the other product of lecithin: cholesterol acyltransferase activity. Possible mechanisms involved in complex formation in the presence of lysophosphatidyl choline are discussed with reference to available information on the effects of lysophosphatidyl choline on lipid and protein organization and conformation.

Key Words:

• Discoidal high density complexes
• electron microscopy
• phospholipid-protein interaction
• ultracentrifugation