5DUV: Crystal Structure Of The Human Galectin-4 N-terminal Carbohydrate Recognition Domain In Complex With Lactose

Citation:
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, alpha-GalNAc/alpha-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.
PDB ID: 5DUVDownload
MMDB ID: 136583
PDB Deposition Date: 2015/9/21
Updated in MMDB: 2016/02
Experimental Method:
x-ray diffraction
Resolution: 1.9  Å
Source Organism:
Similar Structures:
Biological Unit for 5DUV: monomeric; determined by software (PISA)
Molecular Components in 5DUV
Label Count Molecule
Protein (1 molecule)
1
Galectin-4(Gene symbol: LGALS4)
Molecule annotation
Chemicals (3 molecules)
1
2
2
1
* Click molecule labels to explore molecular sequence information.

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