Possible functional interactions of apolipoprotein B-100 segments that associate with cell proteoglycans and the...

The interaction of apoE lipoproteins with cells appears to be mediated by an association with basic sequences of proteoglycans and the apoB/E receptor. ApoB-100 has basic sequences, homologous with those of apoE, that form part of the apoB/E receptor-binding domain. These sequences of apoB-100 also interact with proteoglycans. We investigated whether such segments, in analogy with apoE, could act cooperatively on LDL interactions with proteoglycans and the receptor. As a model we used the two most basic regions of apoB-100, 3147 through 3157 and 3359 through 3367, connected by three glycines (3145-3157-GGG-3359-3367). Such segments may be proximal in LDL by the presence of a disulfide bridge between Cys(3167) and Cys(3297). The apoB heterodimer but not the separated monomers inhibited 125I-LDL degradation in fibroblasts and THP-1 cells by 50% at approximately 11 mumol/L. The heterodimer affinity with arterial proteoglycans was closer to that of LDL and higher than that of the individual peptides. The heterodimer appears to bind specifically to THP-1 cells, with a Kd of 6.2 x 10(-8) mol/L and a Bmax of 1.3 x 10(6) molecules/cell. Monoclonal antibody C-7, which recognizes the apoB receptor, inhibited the binding to cells. Treatment of fibroblasts with chondroitinase ABC or chlorate decreased 125I-LDL degradation markedly. Hydrolysis of pericellular proteoglycans of fibroblasts by chondroitinases reduced mostly the low-affinity, high-capacity component of LDL binding. This compartment appears to hold 70% of the cell-associated LDL when internalization is inhibited at 4 degrees C. Therefore, cell-surface chondroitin sulfate/dermatan sulfate proteoglycans appear to modulate binding and receptor-mediated internalization of LDL. This may be caused, at least in part, by the association of proteoglycans with the apoB-100 segments 3145 through 3157 and 3359 through 3367.