TY - JOUR
T1 - Novel carbohydrate specificity of the 16-kDa galectin from Caenorhabditis elegans
T2 - Binding to blood group precursor oligosaccharides (type 1, type 2, Tα, and Tβ) and gangliosides
AU - Ahmed, Hafiz
AU - Bianchet, Mario A.
AU - Mario Amzel, L.
AU - Hirabayashi, Jun
AU - Kasai, Ken Ichi
AU - Giga-Hama, Yuko
AU - Tohda, Hideki
AU - Vasta, Gerardo R.
N1 - Funding Information:
Supported by grant no. 95-31 from the Lucille P. Markey Trust Fund and grant MCB-00-77928 from the National Science Foundation to G.R.V. and grant 1P01GM51362 from the National Institute of General Medical Sciences to L.M.A. We thank Ms. Sachiko Yamamoto for expert technical assistance.
PY - 2002/8
Y1 - 2002/8
N2 - 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 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, 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 Glu67 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.
AB - 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 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, 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 Glu67 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.
KW - 16-kDa galectin
KW - C.Elegans
KW - Gangliosides
KW - Specificity
KW - Type 1, Type 2, Tα, Tβ blood group
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U2 - 10.1093/glycob/cwf052
DO - 10.1093/glycob/cwf052
M3 - Article
C2 - 12145186
AN - SCOPUS:0036668095
SN - 0959-6658
VL - 12
SP - 451
EP - 461
JO - Glycobiology
JF - Glycobiology
IS - 8
ER -