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 beta-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 cellmatrix interaction, malignant transformation, and cell adhesion. N-CRD shows strong affinity for a23-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 a23-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. Database The atomic coordinates and structure factors of G8NullLac, G8Null2Lac, G8NullSiaLacLac, G8N-free and G8NSiaLacNAc have been deposited in the Protein Data Bank under the accession codes 4FQZ, 3VKL, 3VKM, 3VKN, and 3VKO, respectively. Structured digital abstract G8 and G8 bind by x-ray crystallography (View interaction)