4YLZ

Crystal structure of the human galectin-4 C-terminal carbohydrate recognition domain in complex with lacto-N-neotetraose (LNnT)

Summary for 4YLZ

• Entry DOI: 10.2210/pdb4ylz/pdb
• Related: 4YM0 4YM1 4YM2 4YM3
• Descriptor: Galectin-4, beta-D-galactopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-3)-beta-D-galactopyranose-(1-4)-beta-D-glucopyranose, GLYCEROL, ... (5 entities in total)
• Functional Keywords: galectin, lectin, sugar binding protein, carbohydrate binding protein, lacto-n-neotetraose, carbohydrate recognition, beta sandwich, glycosphingolipid
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 4
• Total formula weight: 71348.16

Authors

Bum-Erdene, K.,Blanchard, H. (deposition date: 2015-03-06, release date: 2015-07-01, Last modification date: 2023-09-27)

Primary citation

Bum-Erdene, K.,Leffler, H.,Nilsson, U.J.,Blanchard, H.
Structural characterization of human galectin-4 C-terminal domain: elucidating the molecular basis for recognition of glycosphingolipids, sulfated saccharides and blood group antigens.
Febs J., 282:3348-3367, 2015

PubMed Abstract: Human galectin-4 is a lectin that is expressed mainly in the gastrointestinal tract and exhibits metastasis-promoting roles in some cancers. Its tandem-repeat nature exhibits two distinct carbohydrate recognition domains allowing crosslinking by simultaneous binding to sulfated and non-sulfated (but not sialylated) glycosphingolipids and glycoproteins, facilitating stabilization of lipid rafts. Critically, galectin-4 exerts favourable or unfavourable effects depending upon the cancer. Here we report the first X-ray crystallographic structural information on human galectin-4, specifically the C-terminal carbohydrate recognition domain of human (galectin-4C) in complex with lactose, lactose-3'-sulfate, 2'-fucosyllactose, lacto-N-tetraose and lacto-N-neotetraose. These structures enable elucidation of galectin-4C binding fine-specificity towards sulfated and non-sulfated lacto- and neolacto-series sphingolipids as well as to human blood group antigens. Analysis of the lactose-3'-sulfate complex structure shows that galectin-4C does not recognize the sulfate group using any specific amino acid, but binds the ligand nonetheless. Complex structures with lacto-N-tetraose and lacto-N-neotetraose displayed differences in binding interactions exhibited by the non-reducing-end galactose. That of lacto-N-tetraose points outward from the protein surface whereas that of lacto-N-neotetraose interacts directly with the protein. Recognition patterns of human galectin-4C towards lacto- and neolacto-series glycosphingolipids are similar to those of human galectin-3; however, detailed scrutiny revealed differences stemming from the extended binding site that offer distinction in ligand profiles of these two galectins. Structural characterization of the complex with 2'-fucosyllactose, a carbohydrate with similarity to the H antigen, and molecular dynamics studies highlight structural features that allow specific recognition of A and B antigens, whilst a lack of interaction with the 2'-fucose of blood group antigens was revealed.

PubMed: 26077389
DOI: 10.1111/febs.13348

Experimental method

X-RAY DIFFRACTION (2.1 Å)