Involvement of sugars in protein-protein interactions

In a cell there is an intricate machinery involved in the biosynthesis of c omplex oligosaccharides of glycoproteins, glycolipids, and proteoglycans. T hese oligosaccharides play important roles in several biological processes, including the folding and transport of glycoproteins across cellular compa rtments. Defective glycan synthesis has been shown to have serious patholog ical consequences and result in several human diseases. The oligosaccharide moieties bind to cellular proteins with high specificity and modulate the homo- and heterodimerization of glycoproteins. Owing to the conformational flexibility of oligosaccharides, the torsional angles of a disaccharide uni t, particularly around the 1-6-linkage, adjust in such a way that the side groups of the oligosaccharides orient themselves in a manner that promotes favorable interactions with the binding residues of the protein. Branched o ligosaccharides cross-link proteins and generate infinite networks of prote in-carbohydrate complexes, resulting in the modulation of various cell resp onses. Glycosaminoglycans, the oligosaccharide moieties of proteoglycans, b ind growth factors with a high degree of specificity and induce interaction s with growth factor receptors, thereby regulating their biological activit y. Using an experimental model system to study the sugar mediated protein-p rotein interactions, we are investigating the sugar ligand-dependent intera ctions between or-Lactalbumin (alpha-LA) and beta-1,4-galactosyltransferase (beta 4Gal-T). Also, using a molecular modeling method, we are investigati ng the heparin dependent dimerization of fibroblast growth factor and growt h factor receptor. Our results, together with studies from various other la boratories, support the hypothesis that in the oligosaccharide induced reco gnition process, sugars accelerate the assembly of the complex by positioni ng and orienting the molecules in an optimal fashion that brings about spec ific protein-protein or protein-carbohydrate interactions. (C) 2000 Elsevie r Science Ltd. All rights reserved.