title: Polymorphisms of mouse apolipoprotein A-II alter its physical and functional nature.
abstract: ApoA-II is the second most abundant protein on HDL making up ∼ 20% of the total protein but its functions have still only been partially characterized. Recent methodological improvements have allowed for the recombinant expression and characterization of human apoA-II which shares only 55% sequence homology with murine apoA-II. Here we describe the purification of the two most common polymorphic variants of apoA-II found in inbred mouse strains, differing at 3 amino acid sites. C57BL/6 mice having variant apoA-II(a) have lower plasma HDL levels than FVB/N mice that have variant apoA-II(b). Characterization of the helical structure of these two variants reveals a more alpha-helical structure for the FVB/N apoA-II. These changes do not alter the lipid or HDL binding of the two apoA-II variants, but significantly increase the ability of the FVB/N variant to promote both ABCA1 and ABCG1 mediated cellular cholesterol efflux. These differences may be differentially altering plasma HDL apoA-II levels. In vivo, neither C57 nor FVB apoA-II protein levels are affected by the absence of apoE, while an apoE/apoA-I double deficiency results in a 50% decrease of plasma FVB apoA-II but results in undetectable levels of C57 apoA-II in the plasma. FVB apoA-II is able to form an HDL particle in the absence of apoE or apoA-I.
authors: Department of Pathology, University of Chicago, Chicago, Illinois, United States of America.
authors: Timothy J
authors: TJ
authors: Sontag
authors: Department of Pathology, University of Chicago, Chicago, Illinois, United States of America.
authors: Catherine A
authors: CA
authors: Reardon
mesh_terms: D000818:Animals; D016633:Apolipoprotein A-II / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D001692:Biological Transport; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D002942:Circular Dichroism; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry; D005260:Female; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011110:Polymorphism, Genetic; D011994:Recombinant Proteins / Q000378:metabolism; D020349:Surface Plasmon Resonance; D053835:Unilamellar Liposomes / Q000737:chemistry
chemical_list: D016633:Apolipoprotein A-II; D008075:Lipoproteins, HDL; D011994:Recombinant Proteins; D053835:Unilamellar Liposomes; D002784:Cholesterol; D004134:Dimyristoylphosphatidylcholine