Multivalent protein-carbohydrate interactions. A new paradigm for supermolecular assembly and signal transduction

Many biological recognition processes involve the binding and clustering of ligand-receptor complexes and concomitant signal transduction events, Such interactions have recently been observed in human T cells in which binding and cross-linking of specific glycoprotein counter-receptors on the surfac e of the cells by an endogenous bivalent carbohydrate binding protein (gale ctin-1) leads to apoptosis [Pace, K. E., et al.(1999) J. Immunol. 163, 3801 -3811]. Importantly, different counter-receptors associated with specific p hosphatase or kinase activities were shown to form separate clusters on the surface of the cells as a result of galectin-1 binding to the carbohydrate moieties of the respective glycoproteins. This suggests that the unique se paration and organization of signaling molecules that results from galectin -1 binding is involved in delivering the signal to die. The ability of gale ctin-1 to induce the separation of specific glycoprotein receptors was mode led on the basis of molecular and structural studies of the binding of mult ivalent carbohydrates to lectins that result in the formation of specific t wo- and three-dimensional cross-linked lattices. These latter studies have been recently highlighted by X-ray crystallographic results showing that a single tetravalent lectin forms distinct cross-linked complexes with four d ifferent bivalent oligosaccharides [Olsen, L. R., et al. (1997) Biochemistr y 36, 15073-15080]. In this report, binding and cross-linking of multivalen t carbohydrates with multivalent lectins is shown to be a new paradigm for supermolecular assembly and signal transduction in biological systems.