Closely related mammals have distinct asialoglycoprotein receptor carbohydrate specificities.
We recently reported that the rat asialoglycoprotein receptor binds oligosaccharides terminating with sialic acid (Sia) alpha2,6GalNAc. Despite a high percentage of identical amino acids in their sequences, orthologues of the asialoglycoprotein receptor (ASGP-R) in different mammals differ in their specificity for terminal Siaalpha2,6GalNAc. The recombinant subunit 1 of the ASGP-R from the rat (RHL-1 or rat hepatic lectin) and the mouse (MHL-1 or mouse hepatic lectin), which differ at only 12 positions in the amino acid sequence of their carbohydrate recognition domains, binds Siaalpha2,6GalNAcbeta1,4GlcNAcbeta1,2Man-bovine serum albumin and GalNAcbeta1,4GlcNAcbeta1,2Man-bovine serum albumin in ratios of 16:1.0 and 1.0:1.0, respectively. Mutagenesis was used to show that amino acids both in the immediate vicinity of the proposed binding site for terminal GalNAc and on the alpha2 helix that is distant from the binding site contribute to the specificity for terminal Siaalpha2,6GalNAc. Thus, multiple amino acid sequence alterations in two key locations contribute to the difference in specificity observed for the rat and mouse ASGP-Rs. We hypothesize that the altered specificity of ASPG-R orthologues in such evolutionarily closely related species reflects rapidly changing requirements for recognition of endogenous or exogenous oligosaccharides in vivo.
Park
Eric I
EI
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Baenziger
Jacques U
JU
D000595:Amino Acid Sequence; D000818:Animals; D037263:Asialoglycoprotein Receptor / Q000737:chemistry*; D001665:Binding Sites; D002241:Carbohydrates / Q000737:chemistry*; D002417:Cattle; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002645:Chickens; D006801:Humans; D037102:Lectins / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009154:Mutation; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011817:Rabbits; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry; D013045:Species Specificity; D013552:Swine
D037263:Asialoglycoprotein Receptor; D002241:Carbohydrates; D037102:Lectins; D011994:Recombinant Proteins