Structures of W77F/W212F and W77F/W212F Toxascaris leonine galectin complex with glucose.

Galectins are glycan-binding proteins (GBPs) characterized by conserved carbohydrate recognition domains (CRDs). Galectin-9, which contains two CRDs, regulates immune responses through interactions with glycoproteins. However, the full-length structure of galectin-9 remains unresolved. Toxascaris leonina galectin (Tl-gal), a homolog of human galectin-9 with ∼35 % sequence identity, shares a similar overall structure, including conserved residues like tryptophan. In Tl-gal, the W77 and W212 residues are directly involved in carbohydrate binding. Here, we present the crystal structures of the Tl-gal W77F/W212F mutant in apo form or complexed with glucose. Comparative structural analysis revealed that mutation of these tryptophan residues induces conformational changes in the overall structure of Tl-gal. These findings underscore the critical role played by conserved tryptophan residues in maintaining galectin structure and glycan-binding function.