DIFFERENTIAL LIGAND-BINDING BY 2 SUBUNITS OF THE RAT-LIVER ASIALOGLYCOPROTEIN RECEPTOR

The rat liver asialoglycoprotein receptor consists of two types of sub units, 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 sub units in the RHL oligomer are not known, The carbohydrate-recognition domain of RHL-2/3 has been prepared by limited proteolysis of the live r receptor so that its properties can be compared with those of the co rresponding domain of RHL-1 previously produced in a bacterial express ion system, Binding studies indicate that while RHL-1 binds N-acetylga lactosamine with approximately 60-fold higher affinity than it binds g alactose, RHL-2/3 has only 2-fold selectivity for N-acetylgalactosamin e. In general, the pattern of monosaccharide-binding specificity for R HL-2/3 is similar to RHL-1, but the discrimination of various sugars r elative 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.