title: Structural characterisation of human galectin-4 N-terminal carbohydrate recognition domain in complex with glycerol, lactose, 3'-sulfo-lactose, and 2'-fucosyllactose.
abstract: Galectin-4 is a tandem-repeat galectin with two distinct carbohydrate recognition domains (CRD). Galectin-4 is expressed mainly in the alimentary tract and is proposed to function as a lipid raft and adherens junction stabilizer by its glycan cross-linking capacity. Galectin-4 plays divergent roles in cancer and inflammatory conditions, either promoting or inhibiting each disease progression, depending on the specific pathological condition. The study of galectin-4's ligand-binding profile may help decipher its roles under specific conditions. Here we present the X-ray structures of human galectin-4 N-terminal CRD (galectin-4N) bound to different saccharide ligands. Galectin-4's overall fold and its core interactions to lactose are similar to other galectin CRDs. Galectin-4N recognises the sulfate cap of 3'-sulfated glycans by a weak interaction through Arg45 and two water-mediated hydrogen bonds via Trp84 and Asn49. When galectin-4N interacts with the H-antigen mimic, 2'-fucosyllactose, an interaction is formed between the ring oxygen of fucose and Arg45. The extended binding site of galectin-4N may not be well suited to the A/B-antigen determinants, α-GalNAc/α-Gal, specifically due to clashes with residue Phe47. Overall, galectin-4N favours sulfated glycans whilst galectin-4C prefers blood group determinants. However, the two CRDs of galectin-4 can, to a less extent, recognise each other's ligands.
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast Campus, Queensland 4222, Australia.
authors.forename: Khuchtumur
authors.initials: K
authors.lastname: Bum-Erdene
authors.affiliation: Section MIG, Department of Laboratory Medicine, Lund University, BMC-C1228b, Klinikgatan 28, SE-22184 Lund, Sweden.
authors.forename: Hakon
authors.initials: H
authors.lastname: Leffler
authors.affiliation: Centre for Analysis and Synthesis, Department of Chemistry, Lund University, PO Box 124, SE-22100 Lund, Sweden.
authors.forename: Ulf J
authors.initials: UJ
authors.lastname: Nilsson
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast Campus, Queensland 4222, Australia.
authors.forename: Helen
authors.initials: H
authors.lastname: Blanchard
mesh_terms: D037541:Galectin 4 / Q000737:chemistry* / Q000378:metabolism; D005990:Glycerol / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007785:Lactose / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008968:Molecular Conformation; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D014312:Trisaccharides / Q000737:chemistry* / Q000378:metabolism
chemical_list: D037541:Galectin 4; D014312:Trisaccharides; D007785:Lactose; D005990:Glycerol; C031420:2'-fucosyllactose
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