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Structural characterisation of human galectin-4 N-terminal carbohydrate recognition domain in complex with glycerol, lactose, 3'-sulfo-lactose, and 2'-fucosyllactose.

<div class='caption-title'>Structure of galectin-4N.</div>
<div class='caption-title'>Crystal structure of galectin-4N-glycerol complex.</div>
<div class='caption-title'>Crystal structure of galectin-4N-lactose complex.</div>
Bum-Erdene K, Leffler H, Nilsson UJ, Blanchard H
OpenAccess logo Sci Rep 6 20289 (2016)
Related entries: 5duu, 5duv, 5duw

Cited: 22 times
EuropePMC logo PMID: 26828567

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.

Articles - 5dux mentioned but not cited (2)

  1. The human milk oligosaccharides 2'-fucosyllactose and 6'-sialyllactose protect against the development of necrotizing enterocolitis by inhibiting toll-like receptor 4 signaling. Sodhi CP, Wipf P, Yamaguchi Y, Fulton WB, Kovler M, Niño DF, Zhou Q, Banfield E, Werts AD, Ladd MR, Buck RH, Goehring KC, Prindle T, Wang S, Jia H, Lu P, Hackam DJ. Pediatr Res 89 91-101 (2021)
  2. Structural characterisation of human galectin-4 N-terminal carbohydrate recognition domain in complex with glycerol, lactose, 3'-sulfo-lactose, and 2'-fucosyllactose. Bum-Erdene K, Leffler H, Nilsson UJ, Blanchard H. Sci Rep 6 20289 (2016)


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  1. Galectin Targeted Therapy in Oncology: Current Knowledge and Perspectives. Wdowiak K, Francuz T, Gallego-Colon E, Ruiz-Agamez N, Kubeczko M, Grochoła I, Wojnar J. Int J Mol Sci 19 E210 (2018)
  2. Extracellular heparan sulfate proteoglycans and glycan-binding lectins orchestrate trans-synaptic signaling. Rushton E, Kopke DL, Broadie K. J Cell Sci 133 jcs244186 (2020)
  3. Modulation of the Gal-9/TIM-3 Immune Checkpoint with α-Lactose. Does Anomery of Lactose Matter? Bailly C, Thuru X, Quesnel B. Cancers (Basel) 13 6365 (2021)
  4. 3'-sulfated LewisA/C: An oncofetal epitope associated with metaplastic and oncogenic plasticity of the gastrointestinal foregut. Das KK, Brown JW. Front Cell Dev Biol 11 1089028 (2023)

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