Glycan-binding proteins are crucial for a wide range of biological processes. They belong to two distinct groups: lectins and glycosaminoglycan (GAG)-binding proteins (GAGBPs). A member of one group rarely possesses the characteristics of both groups. The human lectin Galectin-3 (Gal-3) is a member of the first group. This project is based on the finding that Gal-3, a lectin, actually possesses characteristics of a GAGBP. The current study investigates these newly-discovered characteristics of Gal-3. The research is integrated with educational activities through an initiative called "From Bench to Blackboard." This initiative introduces glycobiology to high school students and K-12 teachers through lab- and web-based approaches. The anticipated results from the proposed work is revealing hitherto unknown properties of Gal-3 and will inspire new research activities involving Gal-3 and GAGs.
Gal-3 is one of the most extensively studied human lectins but it has never been reported as a GAGBP. However, preliminary data for this study show that Gal-3 binds to sulfated GAGs and proteoglycans. The proposed research elucidates the detailed interactions of Gal-3 with GAGs and proteoglycans. The length and sulfation level of GAGs, that are optimal for binding by Gal-3, are determined by calorimetry and spectroscopy. The GAG binding site of Gal-3 is being delineated with the use of site directed mutagenesis. Various biophysical techniques are employed to study non-covalent cross-linking of Gal-3 by GAGs and proteoglycans. In addition, competitive cross-linking of Gal-3 by GAGs and glycoproteins is also being examined. Information obtained from this research is redefining the binding properties of Gal-3 and providing a foundation for discovering Gal-3 dependent cellular and extracellular functions of GAGs and proteoglycans.
