Topsy-turvy binding of negatively charged homogalacturonan oligosaccharides to galectin-3
| Autor: | Xuejiao Xu, Michelle C. Miller, Jie Geng, Tao Zhang, Yi Zheng, Kevin H. Mayo, Yifa Zhou, Guihua Tai, Jiyong Su, Maksim Mayzel |
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| Rok vydání: | 2020 |
| Předmět: |
Models
Molecular chemistry.chemical_classification Magnetic Resonance Spectroscopy biology Stereochemistry Glycoconjugate Galectin 3 Oligosaccharides Lectin Heparan sulfate Oligosaccharide Carbohydrate Crystallography X-Ray Biochemistry chemistry.chemical_compound Residue (chemistry) chemistry Galactose biology.protein Humans Galectin |
| Zdroj: | Glycobiology. 31:341-350 |
| ISSN: | 1460-2423 |
| DOI: | 10.1093/glycob/cwaa080 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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