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Crystal structure of human galectin-9 N-terminal CRD in complex with lactoseCrystal structure of human galectin-9 N-terminal CRD in complex with lactose
Structural highlights
FunctionLEG9_HUMAN Binds galactosides. Has high affinity for the Forssman pentasaccharide. May play a role in thymocyte-epithelial interactions relevant to the biology of the thymus. Inhibits cell proliferation. It is a ligand for HAVCR2/TIM3. Induces T-helper type 1 lymphocyte (Th1) death. Isoform Short acts as an eosinophil chemoattractant.[1] [2] [3] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedGalectins are a family of beta-galactoside-binding lectins that contain a conserved carbohydrate recognition domain (CRD). They exhibit high affinities for small beta-galactosides as well as variable binding specificities for complex glycoconjugates. Structural and biochemical analyses of the mechanism governing specific carbohydrate recognition provide a useful template to elucidate the function of these proteins. Here we report the crystal structures of the human galectin-9 N-terminal CRD (NCRD) in the presence of lactose and Forssman pentasaccharide. Mouse galectin-9 NCRD, the structure of which was previously solved by our group, forms a non-canonical dimer in both the crystal state and in solution. Human galectin-9 NCRD, however, exists as a monomer in crystals, despite a high sequence identity to the mouse homologue. Comparative frontal affinity chromatography analysis of the mouse and human galectin-9 NCRDs revealed different carbohydrate binding specificities, with disparate affinities for complex glycoconjugates. Human galectin-9 NCRD exhibited a high affinity for Forssman pentasaccharide; the association constant for mouse galectin-9 NCRD was 100-fold less than that observed for the human protein. The combination of structural data with mutational studies demonstrated that non-conserved amino acid residues on the concave surface were important for determination of target specificities. The human galectin-9 NCRD exhibited greater inhibition of cell proliferation than the mouse NCRD. We discuss the biochemical and structural differences between highly homologous proteins from different species. Structural analysis of the human galectin-9 N-terminal carbohydrate recognition domain reveals unexpected properties that differ from the mouse orthologue.,Nagae M, Nishi N, Nakamura-Tsuruta S, Hirabayashi J, Wakatsuki S, Kato R J Mol Biol. 2008 Jan 4;375(1):119-35. Epub 2007 Sep 26. PMID:18005988[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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