X-ray structures of human galectin-9 C-terminal domain in complexes with a biantennary oligosaccharide and sialyllactose.
Galectin-9, a tandem-repeat-type β-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 μM) and linear β1-3-linked poly-N-acetyllactosamines (0.09-8.3 μM) and significant affinity for the α2-3-sialylated oligosaccharides (17-34 μM). 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 α2-3-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 α2-3-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.
Yoshida
Hiromi
H
Life Science Research Center, Faculty of Medicine, Kagawa University, 1750-1, Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
Teraoka
Misa
M
Nishi
Nozomu
N
Nakakita
Shin-ichi
S
Nakamura
Takanori
T
Hirashima
Mitsuomi
M
Kamitori
Shigehiro
S
D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D037161:Galectins / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D007785:Lactose / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D012794:Sialic Acids / Q000737:chemistry* / Q000378:metabolism*
D037161:Galectins; C105032:LGALS9 protein, human; D009844:Oligosaccharides; D012794:Sialic Acids; C000020:N-acetylneuraminoyllactose; D007785:Lactose