Structural analysis of the human galectin-9 N-terminal carbohydrate recognition domain reveals unexpected properties that differ from the mouse orthologue.

摘要: Galectins are a family of beta-galactoside-binding lectins that contain conserved carbohydrate recognition domain (CRD). They exhibit high affinities for small beta-galactosides as well variable binding specificities complex glycoconjugates. Structural and biochemical analyses the mechanism governing specific provide useful template to elucidate function these proteins. Here we report crystal structures human galectin-9 N-terminal CRD (NCRD) in presence lactose Forssman pentasaccharide. Mouse NCRD, structure which was previously solved by our group, forms non-canonical dimer both state solution. Human however, exists monomer crystals, despite sequence identity mouse homologue. Comparative frontal affinity chromatography analysis NCRDs revealed different specificities, with disparate NCRD exhibited pentasaccharide; association constant 100-fold less than observed protein. The combination structural data mutational studies demonstrated non-conserved amino acid residues on concave surface were important determination target specificities. greater inhibition cell proliferation NCRD. We discuss differences between highly homologous proteins from species.