Differential ligand binding by two subunits of the rat liver asialoglycoprotein receptor.
The rat liver asialoglycoprotein receptor consists of two types of subunits, a predominant polypeptide designated rat hepatic lectin 1 (RHL-1) and a minor polypeptide, RHL-2/3, that comes in two differentially glycosylated forms. The exact stoichiometry and arrangement of the subunits in the RHL oligomer are not known. The carbohydrate-recognition domain of RHL-2/3 has been prepared by limited proteolysis of the liver receptor so that its properties can be compared with those of the corresponding domain of RHL-1 previously produced in a bacterial expression system. Binding studies indicate that while RHL-1 binds N-acetylgalactosamine with approximately 60-fold higher affinity than it binds galactose, RHL-2/3 has only 2-fold selectivity for N-acetylgalactosamine. In general, the pattern of monosaccharide-binding specificity for RHL-2/3 is similar to RHL-1, but the discrimination of various sugars relative to galactose is reduced substantially. Limited proteolysis and crosslinking studies demonstrate that RHL-2/3 is easily removed from the RHL oligomer in detergent solution and that RHL-1 remains at least trimeric following removal of RHL-2/3. These studies suggest that RHL-1 forms a ligand-binding core while RHL-2/3 acts more as an accessory subunit contributing to selective binding of certain oligosaccharide structures.
Ruiz
N I
NI
Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
Drickamer
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K
D000595:Amino Acid Sequence; D000818:Animals; D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins / Q000378:metabolism*; D001665:Binding Sites; D003432:Cross-Linking Reagents; D008024:Ligands; D008099:Liver / Q000737:chemistry*; D008969:Molecular Sequence Data; D009005:Monosaccharides / Q000494:pharmacology; D010446:Peptide Fragments / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism*; D011487:Protein Conformation; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D014357:Trypsin / Q000378:metabolism
D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins; D003432:Cross-Linking Reagents; D008024:Ligands; D009005:Monosaccharides; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D014357:Trypsin