A Cross-Linking Study of Apo-Low Density Lipoprotein

Chemical cross-linking with dimethylsuberimidate was applied to the study of apo B interactions in human serum low density lipoprotein (LDL). Since apo B is known to have a mass of 500,000 to 600,000 daltons in non-ionic detergent solutions (i.e., a dimer of apo B based on the molecular weight of 260,000 for a single peptide of apo B), the possibility was investigated that the cross-linking reagent might be used to identify the interacting site of apo B in LDL. Although extensive cross-linking was observed in our experiment most of the reaction took place not between apo B's in one LDL (intramolecular) but between apo B's of different LDL's (intermolecular). Only a small fraction of cross-linked apo B dimer was formed intramolecularly. We interpret the results as indicating that the exposed or hydrophilic regions of LDL are scattered on the surface of LDL and that the protein-protein interaction site is not accessible to dimethylsuberimidate, probably being hidden under the surface layer of LDL.