The oligosaccharide chains of glycoproteins and glycolipids of normal and transformed cells have been implicated as receptors in a variety of biological processes including cellular recognition and adhesion, differentiation, and oncogenic transformation. Although the structures of many of the carbohydrates have been determined, little is known about their molecular binding properties, other than their interactions with glycosylases, which regulate their biosynthesis, and lectins, which are carbohydrate binding proteins. Lectins are found in plants, bacteria, and normal and transformed animal cells. Lectin binding to the surface of cells often leads to cross-linking of glycoconjugate receptors, including glycoproteins and glycolipids, which, in many cases, is related to the biological responses of the cells. Recently, we have shown that certain oligosaccharides isolated from glycoproteins and glycolipids are multivalent and can cross-link and precipitate with lectins. We have demonstrated that this leads to an important new dimension of specificity in carbohydrate-protein interactions: namely, the formation of a unique, homogeneous cross-linked complex between each carbohydrate and lectin, even in the presence of mixtures of the molecules. Furthermore, the precipitates are often crystalline and can be investigated by electron microscopy and x-ray diffraction techniques. Our preliminary studies demonstrate that information on the structures of carbohydrate-lectin cross-linked complexes can be obtained, including the symmetries, and geometries of the lattice, the conformation of bound carbohydrates, and possible protein-protein interactions that stabilize the lattice. The latter findings suggest that the structures of certain lectins near their carbohydrate binding sites are designed to facilitate these cross-linking interactions. Our results also indicate that lectins form similar lattices with glycoproteins by carbohydrate mediated cross-linking. Thus, the goal of this proposal is a biophysical investigation of the molecular mechanisms of binding and cross- linking of lectins with multivalent oligosaccharides and glycoconjugates. The results, in turn, will provide insight into their interactions in biological systems.
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