AMINO-TERMINUS OF APOLIPOPROTEIN-B SUFFICES TO PRODUCE RECOGNITION OFMALONDIALDEHYDE-MODIFIED LOW-DENSITY-LIPOPROTEIN BY THE SCAVENGER RECEPTOR OF HUMAN MONOCYTE-MACROPHAGES

Malondialdehyde, a product of lipid peroxidation, produces threshold c onversion of low density lipoprotein (LDL) to a form recognized by the type I and type II scavenger receptors of monocyte-macrophages. To in vestigate whether localized domains of human apoB-100 protein provide recognition determinants, rye tested the ability of several different apoB-bearing particles to interact with the scavenger receptor of huma n monocyte-macrophages. Genetically engineered, carboxyl-terminally tr uncated apoB proteins assembled into lipoprotein form were labeled by fluorescent dye. Fluorescence microscopy and quantitative fluorescent spectrophotometry showed that purified particles containing as little as 23% of the apoB amino-terminus were internalized by the scavenger r eceptor after, but not before, malondialdehyde modification. There was no recognition of the particles by the LDL receptor. Similar results were obtained with human plasma LDL homozygous for carboxyl-terminally truncated apoB-45.2. Liposome-incorporated fusion protein containing apoB residues 547-735 displayed specific uptake by the scavenger recep tor without modification by malondialdehyde. In contrast, fusion prote ins containing apoB residues 3029-3132 or a short amino terminal segme nt failed to interact. Thus, primary sequence presented by residues 1- 1084 sufficed to produce recognition of modified LDL by the scavenger receptor. These receptor-combining domains were sequestered when secre ted in lipoprotein form and were expressed upon malondialdehyde modifi cation. When packaged exogenously in liposome form, fusion protein con taining apoB residues 547-735, containing approximately 4% of the prim ary sequence, mediated scavenger receptor-dependent uptake and hydroly sis. Our findings provide an additional function for the amino-termina l region of apoB and demonstrate that primary sequence presented by th e first 23% of apoB-100 protein suffices to produce recognition of mal ondialdehyde-modified LDL by the scavenger receptor of human monocyte- macrophages.