SYNTHETIC COLLAGEN-LIKE DOMAIN DERIVED FROM THE MACROPHAGE SCAVENGER RECEPTOR BINDS ACETYLATED LOW-DENSITY-LIPOPROTEIN IN-VITRO

The bovine macrophage scavenger receptor is a 70 kDa membrane protein that is trimerized on the macrophage cell surface. The receptor binds modified low-density lipoproteins (LDL), The core binding site is loca ted within 22 residues at the C-terminus of the collagen-like domain o f the receptor, The Lys residue at position 337 plays an important rol e in ligand binding. Here, the collagen-like domain was constructed us ing a peptide architecture technique, in which three collagenous pepti de chains were crosslinked at their N-termini, The crosslinked peptide showed a collagen-like structure by circular dichroism and existed ma inly in a monomeric triple helical form as shown by gel exclusion chro matography, The triple-stranded peptide was demonstrated to bind acety lated LDL (Ac-LDL) using regions derived from Gly323 to Lys340 of the natural bovine scavenger receptor, However, a single-stranded peptide with the same amino acid sequence did not bind Ac-LDL, Furthermore, a triple-stranded mutated peptide in which Lys corresponding to Lys337 i n the mother protein was substituted with Ala showed no binding activi ty to Ac-LDL, These results, taken together, indicate that the synthet ic collagen-like peptide has a similar structure to the binding site i n the scavenger receptor, and support the view that the collagen-like domain of the natural scavenger receptor recognizes Ac-LDL.