Structural and functional properties of human and mouse apolipoprotein A-I

Abstract

Mouse and human plasma apolipoprotein A-I (apo A-I m and apo A-I h, respectively) were investigated to compare their molecular properties in solution, their incorporation into palmitoyloleoylphosphatidylcholine-apo A-I (POPC-apo A-I) discoidal complexes, their structural stability in discoidal complexes and high-density lipoproteins (HDL), and their effect on structural rearrangement of discoidal complexes upon interaction with low-density lipoproteins (LDL). Unlike apo A-I h, only minimal concentration-dependent self-association was observed for apo A-I m. While both apo A-I m and apo A-I h formed discoidal complexes of distinct composition and size that reflected reassembly molar ratios of POPC/apo A-I, apo A-I m demonstrated specific deficiencies in formation of larger-sized complexes. Denaturation of both apo A-I m- or apo A-I h-containing complexes and HDL with guanidine hydrochloride (GuHCl) indicated significantly reduced stabilization of apo A-I m by lipid in these particles. Interaction of apo A-I m- or apo A-I h-containing discoidal complexes with human plasma LDL revealed a more extensive conversion of apo A-I m-complexes to smaller species. Mean hydrophobicities and mean hydrophobic moments of amphipathic helical segments in apo A-I m and apo A-I h were compared; differences potentially contributing to differential lipid-binding properties between apo A-I m and apo A-I h were identified. Our results demonstrate differences between apo A-I m and apo A-I h that may contribute to the major changes in plasma HDL distribution and function observed in apo A-I h transgenic mice.