Life Science Research Center and Faculty of Medicine, Kagawa University, Kagawa, Japan.
FEBS J. 2012 Oct;279(20):3937-51. doi: 10.1111/j.1742-4658.2012.08753.x. Epub 2012 Sep 11.
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.
半乳糖凝集素-8 是一种串联重复型 β-半乳糖苷特异性动物凝集素，具有 N 端和 C 端碳水化合物识别结构域（分别为 N-CRD 和 C-CRD），其碳水化合物结合特异性存在差异，参与细胞-基质相互作用、恶性转化和细胞黏附。N-CRD 对 α2-3-唾液酸化寡糖表现出很强的亲和力，这是半乳糖凝集素-8 的特征。C-CRD 通常对寡糖的亲和力较低，但对 N-糖型分支寡糖的亲和力高于 N-CRD。已经有许多对半乳糖凝集素的单一碳水化合物识别结构域（CRD）的结构研究，但尚未报道含有两个 CRD 的半乳糖凝集素的 X 射线结构。在这里，确定了具有两个 CRD 的人半乳糖凝集素-8 的蛋白酶抗性突变体形式以及半乳糖凝集素-8 N-CRD 与 α2-3-唾液酸化寡糖配体复合物的新型假二聚体结构的 X 射线结构。结果表明 N-CRD 和 C-CRD 之间存在特异性差异，并为 CRD 和/或半乳糖凝集素-8 分子的关联提供了新的见解。
