Interaction of apolipoprotein B from human serum low-density lipoprotein with egg yolk phosphatidylcholine and cholesterol.

Abstract

Binary and ternary complexes of apolipoprotein B (apo B) with egg yolk lecithin and with lecithin plus cholesterol have been formed from detergent-lipid-protein mixed micelles. These particles appear to be spherical by negative-stain electron microscopy and contain 510 000 g of protein (2 mol of apo B) complexed with apparent maximum molar ratios of 780:2 (egg yolk lecithin:apo B) and 1300:280:2 (egg yolk lecithin:cholesterol:apo B). The secondary structure as reflected in the circular dichroic spectra is similar to that of holo-LDL2 when only lecithin is bound, but is significantly altered when cholesterol is also present in the complex, suggesting that the molecular organization of the ternary complex formed in the absence of neutral lipids is significantly different from that of the native lipoprotein. A part of the protein (presumably uncharged) has to be incorporated with the lipid acyl chains in a hydrophobic "core" of the spherical particle. However, the relative amounts of apo B exposed to the aqueous solvent and to the hydrophobic interior of the recombined particles depend on the lipid content and also appear to differ from those in LDL2. The results suggest that the manner in which apo B folds is continuously variable, a result consistent with its ability to bind varying amounts of lipid in vivo.