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

Galectins, a family of soluble β-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 carbohydratebinding 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, Galβ1,3GlcNAc, and type 2, Galβ1,4GlcNAc; Tα, Galβ1,3GalNAcα; Tβ, Galβ1,3GalNAcβ) and gangliosides containing the Tβ 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 Galβ1,4GlcNAc) or at C-4 of GalNAc (in Galβ1,3GalNAc), provides the structural basis for this novel carbohydrate specificity.