Unique epitope of apolipoprotein A-I expressed in pre-beta-1 high-density lipoprotein and its role in the catalyzed efflux of cellular cholesterol.
The ability of mouse anti-apolipoprotein A-I (apo A-I) monoclonal antibodies to recognize pre-beta-HDL species in native plasma was determined. An antibody identifying residues 137-144 of the mature protein uniquely recognized pre-beta-1 HDL, an HDL species of low molecular weight implicated in early cholesterol transport from cell membranes to plasma [Castro, G. R., & Fielding, C. J. (1988) Biochemistry 27, 25-29]. Incubation of plasma with this antibody significantly inhibited the efflux of labeled cholesterol from cultured fibroblast monolayers. A second antibody, binding to residues 93-99 of apo A-I, recognized a second pre-beta-HDL species (pre-beta-2 HDL) but not pre-beta-1 HDL and did not inhibit cholesterol efflux. Several other antibodies had broad specificity for HDL (including pre-beta-1 HDL). This research suggests that apo A-I residues 137-144 are adjacent to or part of a structural site in pre-beta-1 HDL active in promoting the efflux of cellular cholesterol and that this site is not exposed in other HDL species.
Fielding
P E
PE
Cardiovascular Research Institute, University of California, San Francisco 94143-0130.
Kawano
M
M
Catapano
A L
AL
Zoppo
A
A
Marcovina
S
S
Fielding
C J
CJ
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D016632:Apolipoprotein A-I / Q000737:chemistry* / Q000276:immunology; D002384:Catalysis; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D000939:Epitopes / Q000032:analysis; D005347:Fibroblasts / Q000378:metabolism; D053442:High-Density Lipoproteins, Pre-beta; D006801:Humans; D008075:Lipoproteins, HDL / Q000737:chemistry* / Q000276:immunology / Q000502:physiology*; D008969:Molecular Sequence Data
D000911:Antibodies, Monoclonal; D016632:Apolipoprotein A-I; D000939:Epitopes; D053442:High-Density Lipoproteins, Pre-beta; D008075:Lipoproteins, HDL; D002784:Cholesterol