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Lectins on cell surfaces mediate cell-cell interactions by combining with complementary carbohydrates on apposing cells. They play a key role in the control of various normal and pathological processes in living organisms.

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During the last decade, there have been enormous advances in our knowledge of glycoproteins and the stage has Keen set for the biotechnological production of many of them for therapeutic use. These advances are reviewed, with special emphasis on the structure and function of the glycoproteins (excluding the proteoglycans). Current methods for structural analysis of glycoproteins are surveyed, as are novel carbohydrate-peptide linking groups, and mono-and oligo-saccharide constituents found in these macromolecules. The possible roles of the carbohydrate units in modulating the physicochemical and biological properties of the parent proteins are discussed, and evidence is presented on their roles as recognition determinants between molecules and cells, or cell and cells. Finally, examples are given of changes that occur in the carbohydrates of soluble and cell-surface glycoproteins during differentiation, growth and malignancy, which further highlight the important role of these substances in health and disease.Among the different types of covalent modifications that newly synthesized proteins undergo in living organisms, none is as common as glycosylation [l-61. It is also the most diverse, both with respect to the kinds of amino acid that are modified and the structures attached. The origins for this diversity are chemical as well as biological. The former results from the ability of monosaccharides to combine with each other in a variety of ways that differ not only in sequence and chain length, but also in anomery (a or p), position of linkages and branching points. Further structural diversification may occur by covalent attachment of sulfate, phosphate, acetyl or methyl groups to the sugars. Therefore, in theory, an enormous variety of glycans, both oligosaccharides and polysaccharides, can be generated from a relatively limited number of monosaccharides. Biological diversity derives from the fact that, whereas proteins are primary gene products, glycans are secondary gene products. As a result, glycosylation is species-and cell-specific, and is determined as well by the structure of the protein backbone and the carbohydrate attachment site. This means that glycosylation of any protein is dependent on the cell or tissue in which it is produced and that the polypeptide encodes information that directs its own pattern of glycosylation.In an individual glycoprotein more than one carbohydrate unit is often present, attached at different positions by either an N-linkage, an 0-linkage or both. Moreover, each attachCorrespondence to N. Sharon,

More than 70 lectins from leguminous plants belonging to different suborders and tribes have been isolated, mostly from seeds, and characterized to varying degrees. Although they differ in their carbohydrate specificities, they resemble each other in their physicochemical properties. They usually consist of two or four subunits (25-30 kDa), each with one carbohydrate binding site. Interaction with carbohydrates requires tightly bound Ca2+ and Mn2+ (or another transition metal). The primary sequences of more than 15 legume lectins have been established by chemical or molecular genetic techniques. They exhibit remarkable homologies, with a significant number of invariant amino acid residues, among them most of those involved in metal binding. The 3-dimensional structures of the legume lectins are similar, too, and are characterized by a high content of beta-sheets and a lack of alpha-helix. The location of the metal and carbohydrate binding sites, established unequivocally in concanavalin A by high resolution X-ray crystallography, appears to be the same in the other legume lectins. Several of the lectin genes have been cloned and expressed in heterologous systems. This opens the way for the application of molecular genetics to the investigation of the atomic structure of the carbohydrate binding sites of the lectins, and of the relationship between their structure and biological activity. The new approaches may also provide information on the mechanisms that control gene expression in plants and on the role of lectins in nature.