Structures and Functions of the Sugar Chains of Glycoproteins.

Abstract

Most proteins within living organisms contain sugar chains. Recent advancements in cell biology have revealed that many of these sugar chains play important roles as signals for cell-surface recognition phenomena in multi-cellular organisms. In order to elucidate the biological information included in the sugar chains and link them with biology, a novel scientific field called 'glycobiology' has been established. This review will give an outline of the analytical techniques for the structural study of the sugar chains of glycoproteins, the structural characteristics of the sugar chains and the biosynthetic mechanism to produce such characteristics. Based on this knowledge, functional aspects of the sugar chains of glycohormones and of those in the immune system will be described to help others understand this new scientific field. Many proteins produced by mammalian cells contain covalently linked sugar chains and are called glycoproteins. However, because of the difficulty of studying the structure of the sugar chain moieties of glycoproteins, their functional aspects have been ignored during the long history of protein research. In contrast to nucleic acids and proteins, many different sugar chains can be formed by using a small number of monosaccharide units. Let us consider the smallest unit of chains: A-B. In the case of protein, only one structure is made when A and B are assigned to, for example, alanine and leucine. In the case of a sugar chain, however, many isomeric structures are formed. Suppose that A and B were assigned to N-acetylglucosamine and mannose, respectively. As shown in Fig. 1, N-acetylglucosamine can be linked at the four hydroxyl groups of mannose: C-2, C-3, C-4 and C-6. Therefore, four isomeric structures can be formed. Since two anomeric link-HO 0-NHCOCH, Fig. 1. Construction of sugar chains. Correspondence to A. Kobata,

Related effects of cell adaptation to serum-free conditions on murine EPO production and glycosylation by CHO cells

“…N-glycosylation has widely been reported to exert significant effects on several properties of glycoproteins, including antigenicity, solubility, protein folding, protease resistance, pharmacokinetics or biological activity (Schauer 1988;Kobata 1992;Yusa et al 2005). Moreover, sialylation is known to be able to influence the in vivo circulatory lifetime of these proteins, which is crucial to their therapeutic value (Dordal et al 1985;Takeuchi et al 1989;Imai et al 1990;Misaizu et al 1995;Koury 2003;Yuen et al 2003;Elliott et al 2004).…”

Structural analysis and localization of the carbohydrate moieties of a soluble human interferonγreceptor produced in baculovirus‐infected insect cells

“…The soluble receptor was treated with AT-glycosidase F and the oligosaccharides released were analyzed by matrix-assisted laser desorption mass spectrometry, which showed that the protein carried six types of short carbohydrate chains. The predominant species was a hexasaccharide of molecular mass 1,039, containing a fucose subunit linked to the proximal IV-acetylglucosamine residue:Keywords: glycoprotein; glycosylation sites; insect cell-type glycosylation; soluble interferon y receptor Most native proteins carry carbohydrate moieties that fulfill important functions, some of which are still not well understood.Protein glycosylation shows a high structural diversity, and this might be responsible far the diverse and complex roles carbohydrates play in biological and clinical aspects (Paulson, 1989;Goochee et al, 1991;Kobata, 1992;Sharon & Lis, 1993). Development of carbohydrate-based drugs and glycotechnology products in general relies on information derived from recent advances in glycobiology that contributed to elucidation of important carbohydrate functions, like cell-ceJI interaction, protein turnover, protein transport, and others.…”

Using cell engineering and omic tools for the improvement of cell culture processes

“…The functional biological activity of the glycoprotein is directly affected by glycosylation, including its trafficking and folding within the host cell (Scallon et al 2006;Walsh and Jefferis 2006;Willey 1999). Once secreted, solubility, aggregation, stability and immunogenicity of the protein may be affected by its glycosylation pattern (Kobata 1992;Sinclair and Elliott 2005;Willey 1999;Wyss and Wagner 1996). N-glycosylation is initiated in the ER, and O-glycosylation can be initiated in either the ER or Golgi apparatus, but due to processing inconstancies glycans can have frequent structural heterogeneities (Patel et al 1992;Seth et al 2006a;Varki 1998).…”