X-ray structure of a protease-resistant mutant form of human galectin-8 with two carbohydrate recognition domains.
Galectin-8 is a tandem-repeat-type β-galactoside-specific animal lectin possessing N-terminal and C-terminal carbohydrate recognition domains (N-CRD and C-CRD, respectively), with a difference in carbohydrate-binding specificity, involved in cell-matrix interaction, malignant transformation, and cell adhesion. N-CRD shows strong affinity for α2-3-sialylated oligosaccharides, a feature unique to galectin-8. C-CRD usually shows lower affinity for oligosaccharides but higher affinity for N-glycan-type branched oligosaccharides than does N-CRD. There have been many structural studies on galectins with a single carbohydrate recognition domain (CRD), but no X-ray structure of a galectin containing both CRDs has been reported. Here, the X-ray structure of a protease-resistant mutant form of human galectin-8 possessing both CRDs and the novel pseudodimer structure of galectin-8 N-CRD in complexes with α2-3-sialylated oligosaccharide ligands were determined. The results revealed a difference in specificity between N-CRD and C-CRD, and provided new insights into the association of CRDs and/or molecules of galectin-8.
Life Science Research Center and Faculty of Medicine, Kagawa University, Kagawa, Japan.
Hiromi
H
Yoshida
Satoshi
S
Yamashita
Misa
M
Teraoka
Aiko
A
Itoh
Shin-ichi
S
Nakakita
Nozomu
N
Nishi
Shigehiro
S
Kamitori
D000595:Amino Acid Sequence; D001665:Binding Sites / Q000235:genetics; D002240:Carbohydrate Sequence; D002241:Carbohydrates / Q000737:chemistry; D018360:Crystallography, X-Ray; D037161:Galectins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D050505:Mutant Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009844:Oligosaccharides / Q000737:chemistry* / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism; D011485:Protein Binding; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D012794:Sialic Acids / Q000737:chemistry / Q000378:metabolism; D013379:Substrate Specificity
D002241:Carbohydrates; D037161:Galectins; C091991:LGALS8 protein, human; D050505:Mutant Proteins; D009844:Oligosaccharides; D012794:Sialic Acids; D010447:Peptide Hydrolases