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Role of lysines in mediating interaction of modified low density lipoproteins with the scavenger receptor of human monocyte macrophages






Journal of Biological Chemistry 259(18): 11305-11311

Role of lysines in mediating interaction of modified low density lipoproteins with the scavenger receptor of human monocyte macrophages

The ability of the scavenger receptor of human monocyte macrophages to recognize human low density lipoproteins (LDL) progressively modified by 3 lysine-specific reagents, malondialdehyde, acetic anhydride or succinic anhydride, was investigated. Regardless of the reagent utilized, receptor-mediated uptake was dependent upon modification of > 16% of the peptidyl lysines rather than upon the net negative charge of derivatized LDL. Rates of lysosomal hydrolysis of acetyl-LDL and succinyl-LDL increased as a function of progressive modification and reflected the amount of derivatized LDL binding to the receptor. Succinylation or acetylation of > 60% of the lysines was necessary to attain maximal ligand binding, internalization and degradation. In contrast, modification of only 16% of the peptidyl lysines by malondialdehyde resulted in maximal levels of binding, uptake and hydrolysis. The expression of receptor recognition site(s) appears to depend upon the charge modification of critical lysine residues of the LDL protein rather than the net negative charge of the lipoprotein complex. Malondialdehyde, a bufunctional reactant, may modify surface and sequestered lysines concomitantly and thus promote efficient formation of the recognition site(s). [Blood monocytes may be foam cell precursors in atherogenesis.].


Accession: 006351595

PMID: 6088540



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