Molecular and Mechanistic Basis of Lectin-Glycan Interactions

Recognition of glycoconjugates by lectins is critical for many biological processes. Lectins interact with glycans through hydrogen bonding, metal ion coordination, hydrophobic association, van der Waals and ionic interactions. Water molecules in the vicinity of the binding sites and glycan conformation also play roles. Furthermore, the valence of the glycan epitopes and the number and geometry of the binding sites of lectins play important roles in their interactions. Natural glycoconjugates are often multivalent and possess multiple copies of the same glycan epitope. Their multivalent interactions with lectins, which are oligomeric proteins, often enhance the weak binding affinities of a single glycan epitope. Multivalent interactions can be either intramolecular or intermolecular. In the latter case, gradients of microaffinity constants are associated with multivalent carbohydrates binding to lectins. When the valence of either the glycoconjugate or lectin exceeds two, intermolecular multivalent binding can result in lectin-glycoconjugate cross-linking interactions that form either organized or disorganized clustered complexes. Such complexes are involved in signal transduction mechanisms on the surface of cells. Scaffolds, the non-glycan parts of glycoconjugates, do not participate in lectin binding yet they modulate lectin binding interactions. In addition, lectins rarely to bind to sulfated glycosaminoglycans (GAGs) and proteoglycans. The human lectin Galectin-3 has the rare ability to do both. The binding affinity of lectins for linear biopolymers, such as mucins and GAGs, is proportional to the length of the polymers. A model termed “bind-and-jump” presented in this chapter explains how lectins interact with mucins and GAGs.