Structural and functional properties of human and mouse apolipoprotein A-I.
Mouse and human plasma apolipoprotein A-I (apo A-Im and apo A-Ih, 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-Ih, only minimal concentration-dependent self-association was observed for apo A-Im. While both apo A-Im and apo A-Ih formed discoidal complexes of distinct composition and size that reflected reassembly molar ratios of POPC/apo A-I, apo A-Im demonstrated specific deficiencies in formation of larger-sized complexes. Denaturation of both apo A-Im- or apo A-Ih-containing complexes and HDL with guanidine hydrochloride (GuHCl) indicated significantly reduced stabilization of apo A-Im by lipid in these particles. Interaction of apo A-Im- or apo A-Ih-containing discoidal complexes with human plasma LDL revealed a more extensive conversion of apo A-Im-complexes to smaller species. Mean hydrophobicities and mean hydrophobic moments of amphipathic helical segments in apo A-Im and apo A-Ih were compared; differences potentially contributing to differential lipid-binding properties between apo A-Im and apo A-Ih were identified. Our results demonstrate differences between apo A-Im and apo A-Ih that may contribute to the major changes in plasma HDL distribution and function observed in apo A-Ih transgenic mice.
Gong
E L
EL
Life Sciences Division, Lawrence Berkeley Laboratory, University of California, Berkeley 94720.
Tan
C S
CS
Shoukry
M I
MI
Rubin
E M
EM
Nichols
A V
AV
D000818:Animals; D016632:Apolipoprotein A-I / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001692:Biological Transport; D002942:Circular Dichroism; D015870:Gene Expression; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood / Q000737:chemistry*; D008077:Lipoproteins, LDL / Q000097:blood / Q000737:chemistry*; D051379:Mice; D008822:Mice, Transgenic; D013050:Spectrometry, Fluorescence
D016632:Apolipoprotein A-I; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL