X-ray structures of human galectin-9 C-terminal domain in complexes with a biantennary oligosaccharide and sialyllactose.
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Yoshida H, Teraoka M, Nishi N, Nakakita S, Nakamura T, Hirashima M, Kamitori S
X-ray structures of human galectin-9 C-terminal domain in complexes with a biantennary oligosaccharide and sialyllactose.
J Biol Chem. 2010 Nov 19;285(47):36969-76. doi: 10.1074/jbc.M110.163402. Epub 2010 Sep 22.
- PubMed ID
- 20861009 [ View in PubMed]
- Abstract
Galectin-9, a tandem-repeat-type beta-galactoside-specific animal lectin with two carbohydrate recognition domains (CRDs) at the N- and C-terminal ends, is involved in chemoattraction, apoptosis, and the regulation of cell differentiation and has anti-allergic effects. Its ability to recognize carbohydrates is essential for its biological functions. Human galectin-9 (hG9) has high affinity for branched N-glycan-type oligosaccharides (dissociation constants of 0.16-0.70 muM) and linear beta1-3-linked poly-N-acetyllactosamines (0.09-8.3 muM) and significant affinity for the alpha2-3-sialylated oligosaccharides (17-34 muM). Further, its N-terminal CRD (hG9N) and C-terminal CRD (hG9C) differ in specificity. To elucidate this unique feature of hG9, x-ray structures of hG9C in the free form and in complexes with N-acetyllactosamine, the biantennary pyridylaminated oligosaccharide, and alpha2-3-sialyllactose were determined. They are the first x-ray structural analysis of C-terminal CRD of the tandem-repeat-type galectin. The results clearly revealed the mechanism by which branched and alpha2-3-sialylated oligosaccharides are recognized and explained the difference in specificity between hG9N and hG9C. Based on structural comparisons with other galectins, we propose that the wide entrance for ligand binding and the shallow binding site of hG9C are favorable for branched oligosaccharides and that Arg(221) is responsible for recognizing sialylated oligosaccharides.