6KXB

Galectin-3 CRD binds to GalA trimer

Summary for 6KXB

• Entry DOI: 10.2210/pdb6kxb/pdb
• Descriptor: Galectin-3, alpha-D-galactopyranuronic acid-(1-4)-alpha-D-galactopyranuronic acid-(1-4)-beta-D-galactopyranuronic acid (3 entities in total)
• Functional Keywords: galectin-3 crd, gala trimer, sugar binding protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 16247.44

Authors

Su, J. (deposition date: 2019-09-10, release date: 2020-08-26, Last modification date: 2023-11-22)

Primary citation

Zheng, Y.,Su, J.,Miller, M.C.,Geng, J.,Xu, X.,Zhang, T.,Mayzel, M.,Zhou, Y.,Mayo, K.H.,Tai, G.
Topsy-turvy binding of negatively charged homogalacturonan oligosaccharides to galectin-3.
Glycobiology, 31:341-350, 2021

PubMed Abstract: Galectin-3 is crucial to many physiological and pathological processes. The generally accepted dogma is that galectins function extracellularly by binding specifically to β(1→4)-galactoside epitopes on cell surface glycoconjugates. Here, we used crystallography and NMR spectroscopy to demonstrate that negatively charged homogalacturonans (HG, linear polysaccharides of α(1→4)-linked-D-galacturonate (GalA)) bind to the galectin-3 carbohydrate recognition domain. The HG carboxylates at the C6 positions in GalA rings mandate that this saccharide bind galectin-3 in an unconventional, "topsy-turvy" orientation that is flipped by about 180o relative to that of the canonical β-galactoside lactose. In this binding mode, the reducing end GalA β-anomer of HGs takes the position of the nonreducing end galactose residue in lactose. This novel orientation maintains interactions with the conserved tryptophan and seven of the most crucial lactose-binding residues, albeit with different H-bonding interactions. Nevertheless, the HG molecular orientation and new interactions have essentially the same thermodynamic binding parameters as lactose. Overall, our study provides structural details for a new type of galectin-sugar interaction that broadens glycospace for ligand binding to Gal-3 and suggests how the lectin may recognize other negatively charged polysaccharides like glycoaminoglycans (e.g. heparan sulfate) on the cell surface. This discovery impacts on our understanding of galectin-mediated biological function.

PubMed: 32909036
DOI: 10.1093/glycob/cwaa080

Experimental method

X-RAY DIFFRACTION (1.5 Å)