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 lip oprotein (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, c omposition, 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 composi tion and size. SR-BI expressed in transfected Chinese hamster ovary cells w as shown to bind human HDL2 with greater affinity than HDL3, suggesting tha t HDL sine, 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-phosphati dylcholine-containing HDL particles having identical components and equal a mounts of apoA-I, but differing in size (7.8 vs. 9.6 nm in diameter) and ap oA-I conformation. The affinity of binding to SR-BI plas significantly grea ter (50-fold) for the larger (9.6-mm) particle than for the 7.8-nm particle . We conclude that differences in apoA-I conformation in different-sized pa rticles markedly influence apoA-I recognition by SR-BI, Preferential bindin g of larger HDL particles to SR-BI would promote productive selective chole steryl ester uptake from larger cholesteryl ester-rich HDL over lipid-poor HDL.