Apolipoprotein A-I conformation markedly influences HDL interaction with scavenger receptor BI.
Apolipoprotein A-I (apoA-I) is an important ligand for the high density lipoprotein (HDL) scavenger receptor class B type I (SR-BI). SR-BI binds both free and lipoprotein-associated apoA-I, but the effects of particle size, composition, and apolipoprotein conformation on HDL binding to SR-BI are not understood. We have studied the effect of apoA-I conformation on particle binding using native HDL and reconstituted HDL particles of defined composition and size. SR-BI expressed in transfected Chinese hamster ovary cells was shown to bind human HDL(2) with greater affinity than HDL(3), suggesting that HDL size, composition, and possibly apolipoprotein conformation influence HDL binding to SR-BI. To discriminate between these factors, SR-BI binding was studied further using reconstituted l-alpha-palmitoyloleoyl-phosphatidylcholine-containing HDL particles having identical components and equal amounts of apoA-I, but differing in size (7.8 vs. 9.6 nm in diameter) and apoA-I conformation. The affinity of binding to SR-BI was significantly greater (50-fold) for the larger (9.6-nm) particle than for the 7.8-nm particle. We conclude that differences in apoA-I conformation in different-sized particles markedly influence apoA-I recognition by SR-BI. Preferential binding of larger HDL particles to SR-BI would promote productive selective cholesteryl ester uptake from larger cholesteryl ester-rich HDL over lipid-poor HDL.
de Beer
M C
MC
Department of Internal Medicine, University of Kentucky Medical Center, Lexington, KY 40536.
Durbin
D M
DM
Cai
L
L
Jonas
A
A
de Beer
F C
FC
van der Westhuyzen
D R
DR
D016632:Apolipoprotein A-I / Q000737:chemistry*; D018955:CD36 Antigens / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008565:Membrane Proteins; D010316:Particle Size; D011485:Protein Binding; D011487:Protein Conformation; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D011994:Recombinant Proteins / Q000737:chemistry; D051122:Scavenger Receptors, Class B
D016632:Apolipoprotein A-I; D018955:CD36 Antigens; D008075:Lipoproteins, HDL; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D011994:Recombinant Proteins; C495124:SCARB1 protein, human; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B