MODELING THE COMBINING SITE OF THE HUMAN ASIALOGLYCOPROTEIN RECEPTOR

A model for the carbohydrate recognition domain (CRD) and combining si te of the human asialoglycoprotein (ASGP) receptor has been computed o n the basis of the close sequence homology with the mannose-binding le ctin (MBP), whose three-dimensional structure in complex with a ligand has been determined by crystallographic methods (Weis, W.I.; Drickame r, K.; Hendrickson, W.A. Nature 1992, 360: 127). Within the limitation s of modeling methods, the model is compatible with data on ligand bin ding of the family C-type lectins, of which the MBP and the ASGP recep tor are members. The model derived can serve as a guide for designing site-directed mutagenesis experiments in order to further elucidate th e origins of specificity of the ASGP receptor toward galactose. In par ticular, the model focuses attention on the possible role of position 207 (MBP sequence numbering) in promoting galactose binding.