Structural Basis of Galactose Recognition by C-type Animal Lectins

• Published in: The Journal of biological chemistry 1996-03, Vol.271 (12), p.6679-6685
• Main Authors: Kolatkar, A R, Weis, W I
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Galactose - metabolism; Lectins - chemistry; Lectins - genetics; Lectins - metabolism; Molecular Sequence Data; Protein Binding; Protein Conformation; Rats
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.271.12.6679

The asialoglycoprotein receptors and many other C-type (Ca -dependent) animal lectins specifically recognize galactose- or N -acetylgalactosamine-terminated oligosaccharides. Analogous binding specificity can be engineered into the homologous rat mannose-binding protein A by changing three amino acids and inserting a glycine-rich loop (Iobst, S. T., and Drickamer, K.(1994) J. Biol. Chem. 269, 15512-15519). Crystal structures of this mutant complexed with β-methyl galactoside and N -acetylgalactosamine (GalNAc) reveal that as with wild-type mannose-binding proteins, the 3- and 4-OH groups of the sugar directly coordinate Ca and form hydrogen bonds with amino acids that also serve as Ca ligands. The different stereochemistry of the 3- and 4-OH groups in mannose and galactose, combined with a fixed Ca coordination geometry, leads to different pyranose ring locations in the two cases. The glycine-rich loop provides selectivity against mannose by holding a critical tryptophan in a position optimal for packing with the apolar face of galactose but incompatible with mannose binding. The 2-acetamido substituent of GalNAc is in the vicinity of amino acid positions identified by site-directed mutagenesis (Iobst, S. T., and Drickamer, K.(1996) J. Biol. Chem. 271, 6686-6693) as being important for the formation of a GalNAc-selective binding site.