13C nuclear magnetic resonance spectroscopic evidence for hydrophobic lipid-protein interactions in human high density lipoproteins.

Phosphatidylcholines, sphingomyelins, cholesterol, and cholesterol esters were enriched with (13)C by chemical synthesis in specific positions of their hydrophilic groups and aliphatic chains. Their spin-lattice relaxation times were determined in organic solvents. The substances were organized as liposomes and recombined with total human high density apolipoproteins and the two separated main components, apolipoprotein A-I (apoLp-Gln-I) and apolipoprotein A-II (apoLp-Gln-II). These (13)C nuclear magnetic resonance data established that in reassembled high density lipoproteins the phospholipid molecules bind to the apoprotein moieties with their hydrophobic fatty acid chains and not with their hydrophilic zwitterionic groups. Apolipoprotein A-I preferentially binds phosphatidylcholine, although its lipid-binding capacity is smaller than that of apolipoprotein A-II. Apolipoprotein A-II avidly reassembles with sphingomyelin by hydrophobic interactions. A model of the molecular organization of the high density lipoportein particle has been derived.