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.