Novel carbohydrate specificity of the 16-kDa galectin from Caenorhabditis elegans: binding to blood group precursor oligosaccharides (type 1, type 2, T , and T ) and gangliosides

Abstract

Galectins, a family of soluble beta-galactosyl-binding lectins, are believed to mediate cell-cell and cell-extracellular matrix interactions during development, inflammation, apoptosis, and tumor metastasis. However, neither the detailed mechanisms of their function(s) nor the identities of their natural ligands have been unequivocally elucidated. Of the several galectins present in the nematode Caenorhabditis elegans, the 16-kDa "proto" type and the 32-kDa "tandem-repeat" type are the best characterized so far, but their carbohydrate specificities have not been examined in detail. Here, we report the carbohydrate-binding specificity of the recombinant C. elegans 16-kDa galectin and the structural analysis of its binding site by homology modeling. Our results indicate that unlike the galectins characterized so far, the C. elegans 16-kDa galectin interacts with most blood group precursor oligosaccharides (type 1, Galbeta1,3GlcNAc, and type 2, Galbeta1,4GlcNAc; Talpha, Galbeta1,3GalNAcalpha; Tbeta, Galbeta1,3GalNAcbeta) and gangliosides containing the Tbeta structure. Homology modeling of the C. elegans 16-kDa galectin CRD revealed that a shorter loop containing residues 66-69, which enables interactions of Glu(67) with both axial and equatorial -OH at C-3 of GlcNAc (in Galbeta1,4GlcNAc) or at C-4 of GalNAc (in Galbeta1,3GalNAc), provides the structural basis for this novel carbohydrate specificity.

A Galectin of Unique Domain Organization from Hemocytes of the Eastern Oyster (Crassostrea virginica) Is a Receptor for the Protistan Parasite Perkinsus marinus

“…In the C. elegans galectin Lec-6, the absence of these two residues confers broader carbohydrate specificity relative to that of the mammalian prototype galectins (28). The structural analysis of the CvGal CRDs by homology modeling strongly suggested that, although CvGal CRDs bind ␤-galactosyl residues, their specificity for N-acetylated disaccharides and oligosaccharides may differ from the mammalian galectins.…”

The Galectin CvGal1 from the Eastern Oyster (Crassostrea virginica) Binds to Blood Group A Oligosaccharides on the Hemocyte Surface*

“…Solid Phase Binding, Binding Inhibition, and Competitive Inhibition Assays-Solid phase lectin binding assays were carried out as described elsewhere (15,26). Briefly, 96-well microtiter plates were coated with neoglycoproteins, or untreated or glycosidase-treated authentic glycoproteins (10 g/ml in PBS), or hemocyte extracts (0.5 g/ml in PBS) for 3 h at 37°C.…”

Galectin-3 Induces Death of Candida Species Expressing Specific β-1,2-Linked Mannans

“…Recently, it has become apparent that the galectin family of lectins can also participate in the innate immune defense against pathogens (12). Galectins are present in all multicellular organisms, including worms, sponges, multicellular fungi, and insects (13)(14)(15)(16)(17)(18)(19). Galectins are PRRs in several types of organisms, and many mammalian pathogens express saccharide structures that are recognized by galectins.…”