Molecular characterization of the rat Kupffer cell glycoprotein receptor.
The Kupffer cell receptor for glycoproteins has been reported to have a role in clearance of galactose- and fucose-terminated glycoproteins from circulation. Although the gene and a cDNA encoding the receptor have been described, there has been little study of the receptor protein. To address some questions about possible ligands and functions for this receptor, fragments representing portions of the extracellular domain have been expressed and characterized. The extracellular domain consists of a trimer stabilized by an extended coiled-coil of alpha-helices. The receptor displays monosaccharide-binding characteristics similar to the hepatic asialoglycoprotein receptor, but with somewhat less selectivity. The two best monosaccharide ligands are GalNAc and galactose. alpha-Methyl fucoside is a particularly poor ligand. Analysis of Kupffer cell receptor binding to glycoproteins and oligosaccharides released from them reveals highest affinity for desialylated, complex N-linked glycans. The best glycoprotein ligands contain multiple highly branched oligosaccharides. A human ortholog of the rat receptor gene does not encode a full-length protein and is not expressed in liver. These characteristics suggest that the receptor may have functions parallel to those of the hepatocyte asialoglycoprotein receptor in some (but not all) mammalian species.
Fadden
Andrew J
AJ
The Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX21 3QU, United Kingdom.
Holt
Oliver J
OJ
Drickamer
Kurt
K
D000595:Amino Acid Sequence; D000818:Animals; D037263:Asialoglycoprotein Receptor; D006017:Glycolipids / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009005:Monosaccharides / Q000378:metabolism; D009439:Neuraminidase; D009844:Oligosaccharides / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051381:Rats; D011971:Receptors, Immunologic / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D011994:Recombinant Proteins; D016415:Sequence Alignment
D037263:Asialoglycoprotein Receptor; D006017:Glycolipids; D006023:Glycoproteins; C072264:Kupffer cell receptor; D009005:Monosaccharides; D009844:Oligosaccharides; D011971:Receptors, Immunologic; D011994:Recombinant Proteins; D009439:Neuraminidase