The differences in structural specificity for recognition and binding between asialoglycoprotein receptors of liver and macrophages.
The Gal/GalNAc-specific lectin on the surface of rat peritoneal macrophages (macrophage asialoglycoprotein binding protein, M-ASGP-BP), which consists of a single polypeptide chain of 42 kDa, can form a homo-oligomeric receptor exhibiting high affinity for asialoorosomucoid (ASOR) [Ozaki K., Ii M., Itoh N., Kawasaki T. (1992) J Biol Chem 267: 9229-35]. In this study, the binding affinity of M-ASGP-BP was studied by using a series of synthetic or natural glycosides as inhibitors of 125I-ASOR binding to recombinant M-ASGP-BP expressed on COS-1 cells (rM-ASGP-BP), and the results were compared with those of human hepatic lectin (HHL) on Hep G2 cells. Clustering of multiple Gal (or GalNAc) residues increased the binding affinity to M-ASGP-BP as well as to HHL. In contrast to HHL and other mammalian hepatic lectins, rM-ASGP-BP bound Gal residues tighter than GalNAc residues. A galactose-terminated triantennary N-glycoside, having one N-acetyl-lactosamine unit on the 6 branch and two N-acetyl-lactosamine units on the 3 branch of the trimannosyl core structure, showed affinity enhancement of approximately 10(5) over a monovalent ligand for HHL, while the same glycopeptide showed enhancement of about 2000-fold for rM-ASGP-BP. These results suggest that spatial arrangements of sugar combining sites and subunit organization of macrophage and hepatic lectins are different.
D000818:Animals; D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins / Q000378:metabolism*; D002240:Carbohydrate Sequence; D006023:Glycoproteins / Q000737:chemistry; D006801:Humans; D008099:Liver / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D008969:Molecular Sequence Data; D009005:Monosaccharides / Q000737:chemistry; D011869:Radioligand Assay; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins; D006023:Glycoproteins; D009005:Monosaccharides; D011956:Receptors, Cell Surface