AI Article Synopsis
- Galectin-10 (Gal-10) is important for regulating lymph cell functions and forms Charcot-Leyden crystals in the body.
- The crystal structures of Gal-10 and its variants revealed a unique dimer shape that differs from other galectins, and specific interactions within the dimer inhibit disaccharide binding.
- The study found that altering certain key residues, like Trp72, can unexpectedly enhance the agglutination of red blood cells, indicating a complex role in ligand binding specificity.
Article Abstract
Galectin-10 (Gal-10) which forms Charcot-Leyden crystals in vivo, is crucial to regulating lymph cell function. Here, we solved the crystal structures of Gal-10 and eight variants at resolutions of 1.55-2.00 Å. Structural analysis and size exclusion chromatography demonstrated that Gal-10 dimerizes with a novel global shape that is different from that of other prototype galectins (e.g., Gal-1, -2 and -7). In the Gal-10 dimer, Glu33 from one subunit modifies the carbohydrate-binding site of another, essentially inhibiting disaccharide binding. Nevertheless, glycerol (and possibly other small hydroxylated molecules) can interact with residues at the ligand binding site, with His53 being the most crucial for binding. Alanine substitution of the conserved Trp residue (Trp72) that is crucial to saccharide binding in other galectins, actually leads to enhanced erythrocyte agglutination, suggesting that Trp72 negatively regulates Gal-10 ligand binding. Overall, our crystallographic and biochemical results provide insight into Gal-10 ligand binding specificity.
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| http://dx.doi.org/10.1093/glycob/cwx107 | DOI Listing |
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