Structures and Functions of the Sugar Chains of Glycoproteins Akira KOBATA * Most proteins within living organisms contain sugar chains. Recent advanc

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1 Structures and Functions of the Sugar Chains of Glycoproteins Akira KOBATA * Most proteins within living organisms contain sugar chains. Recent advancement of cell biology has revealed that many of these sugar chains play important roles as signals for cell surface recognition phenomena in multi-cellular organisms. Based on an idea to elucidate the biological informations included in the sugar chains and introduce them as knowledge of biology, a novel scientific field called "glycobiology" was established. This review will give an outline of the structural characteristics and biosynthetic mechanism of the Asn-linked sugar chains of glycoproteins. Based on these knowledges, functional aspects of the sugar chains in the immune system of mammals, and of those of human chorionic gonadotropin will be described in order to help readers to access this new scientific field. Key words : Glycoprotein ; Asn-linked sugar chains ; Microheterogeneity ; Concanavalin A ; Exoglycosidase ; Bisecting GlcNAc ; Processing of sugar chains ; N-Acetylglucosaminyltransferases ; Humanchorionic gonadotropin ; Immunoglobulin G. Fig. 1 Construction of sugar chains * Department of Biochemistry Science, the University of Tokyo, the Institute of Medical

2 Fig. 2 Ĉ-elimination reaction of the mucin-type sugar chains of a glycoprotein. S represents a sugar chain. R = H or CH,; R', R"= peptides

3 Fig. 3 General structures of the susceptible sugar chains for endo-ƒà-nacetylglucosaminidases. 1. Endo-ƒÀ-N-acetylglucosaminidase D ; 2. endo-ƒà-n-acetylglucosaminidase H ; 3. endo-ƒà-n-acetylglucosaminidase C11. R represents either hydrogen sugars. or Arrows indicate the positions of hydrolysis. Renovated from A. Kobata, Anal. Biochem, 100, 1 (1977).

4 Fig. 4 The structure recognized by Con A. Table 1 Binding specificities of immobilized lectin columns. R= sugar chains.

5 Fig. 5 Two isomeric pentasaccharides isolatod from human milk. Fig. 6 The subgroups of Asn-linked sugar chains.

6 Fig. 7 Processing in the biosynthesis of Asn-linked sugar chains. R=GleNAc Ĉ1. 4GIcNAc (Asn-X-Ser or Thr) protein.

7 Fig. 8 Maturation of the Asn-linked sugar chains : formation of branching structures of complex type sugar chains. R is the same as in Fig. 7.

8 Fig. 9 Formation of various outer chain moieties R represents the core pentasaccharide linked to a protein.

9 Fig. 10 Major sugar chain structures of y-gtps from the kidneys and the livers of various mammals.

10 Table 2 The Asn-linked sugar chains of the two subunits of hcg.

11

12 1) E. F. Neufeld, G. Ashwell, "The Biochemistry of Glycoproteins & Proteoglycans", ed, by W. J. Lennarz, Plenum Press, Inc., New York, 1980, p.241 2) D. M. Carlson, J. Biol. Chem., 243, 616 (1968) 3) J. Amano, A. Kobata, Methods Enzymol., 179, 261 (1989) 4) J. Amano, R. Nishimura, M. Mochizuki, A. Kobata, J. Biol. Chem., 263, 1157 (1988) 5) J. Amano, P. Staehl, E. G. Berger, N. Kochibe, A. Kobata, ibid., 266, (1991) 6) N. Koide, T. Muramatsu, ibid., 249, 4897 (1974) 7) A. L. Tarentino, F. Maley, ibid., 249, 811 (1974) 8) S. Ito, T. Muramatsu, A. Kobata, Arch, Biochem. Biophys., 171, 78 (1975) 9) S. Takasaki, T. Mizuochi, A. Kobata, Methods

13 Enzymol., 83, 263 (1982) 10) N. Takahashi, Biochem. Biophys. Res. Commun., 76, 1194 (1977) 11) T. H. Plummer, Jr., J.H. Elder, S. Alexander, A. W. Phelan, A.L. Tarentino, J. Biol. Chem., 259, (1984) 12) S. Takasaki, A. Kobata, Methods Enzymol., 50, 50 (1978) 13) S. Yamamoto, S. Hase, S. Fukuda, O. Sano, T. Ikenaka, J. Biochem., 105, 547 (1989) 14) K. Yamashita, T. Mizuochi, A. Kobata, Methods Enzymol., 83, 105 (1982) 17) S. Ogata, T. Muramatsu, A. Kobata, J. Biochem., 78, 687 (1975) 18) A. Kobata, K. Yamashita, Methods Enzymol., 179, 46 (1989) 19) K. Yamashita, K. Totani, T. Ohkura, S. Takasaki, I.J. Goldstein, A Kobata, J. Biol Chem., 262, 1602 (1987) 20) K. Yamashita, N. Kochibe, T. Ohkura, I. Ueda, A. Kobata, ibid., 260, 4688 (1985) 21) K. Yamashita, K. Umetsu, T. Suzuki, Y. Iwaki, T. Endo, A. Kobata, ibid., 263, (1988) 22) H. Harada, M. Kamei, Y. Tokumoto, S. Yui, F. Koyama, N. Kochibe, T. Endo, A. Kobata, Anal Biochem., 164, 374 (1987) 23) A. Kobata, ibid., 100, 1 (1979) 24) A. Kobata, Methods Enzymol, 83, 263 (1982) 25) J.C. Paulson, J. -P. Prieels, L.R. Glasgow, R.L. Hill, J. Biol Chem., 253, 5617 (1978) 26) J.F.G. Vliegenthart, L. Dorland, H. V. Halbeek, "Advances in Carbohydrate Chemistry and Biochemisty", Vol, 41, eds. by R.S. Tipson, D. Horton, Academic Press, New York, 1983, p ) A. Kobata, "27Th International Congress of Pure and Applied Chemisty" ed. by A. Varmavuori, Pergamon Press, New York, 1980, p ) R. Kornfeld, S. Kornfeld, Ann. Rev Biochem., 54, 631 (1985) 29) H. Schachter, S. Narasimhan, P. Gleeson, G. Vella, Gann Monograph on Cancer Res., 29, 177 (1983) 30) K. Yamashita, A. Hitoi, Y. Matsuda, A. Tuji, N. Katunuma, A. Kobata, J. Biol. Chem., 258, 1098 (1983) 31) K. Yamashita, Y. Tachibana, H. Shichi, A. Kobata, J. Biochem., 93, 135 (1983) 32) K. Yamashita, A. Hitoi, N. Tateishi, T. Higashi, Y. Sakamoto, A. Kobata, Arch. Biochem Biophys, 225, 993 (1983) 33) K. Yamashita, A. Hitoi, Y. Matsuda, T. Miura, N. Katunuma, A. Kobata, J. Biochem, 99, 55 (1986) 34) K. Yamashita, A. Hitoi, N. Taniguchi, N. Yokosawa, Y. Tsukada, A. Kobata, Cancer Res., 43, 5059 (1983) 35) K. Yamashita, K. Totani, Y. Iwaki, I. Tanizawa, N. Tateishi, T. Higashi, Y. Sakamoto, A. Kobata, J. Biochem, 105, 728 (1989) 36) K. Yamashita, A. Hitoi, M. Irie, A. Kobata, Arch. Biochem Biophys., 250, 263 (1986) 37) G. Spik, B. Bayard, B. Fournet, G. Strecker, S. Bouquart, J. Montreuil, FEBS Lett., 50, 296 (1975) 38) K. Yamashita, C.-J. Liang, S. Funakoshi, A. Kobata, J. Biol. Chem., 256, 1283 (1981) 39) T. Mizuochi, A. Kobata, Biochem. Biophys. Res. Commun., 97, 772 (1980) 40) A. Kobata, "Glycoprotein Hormones", eds. by W. W. Chin, I. Boime, Norwell, Massachusetts, 1990, p.19 41) T. Kawano, T. Endo, R. Nishimura, T. Mizuochi, M. Mochizuki, N. Kochibe, A. Kobata, Arch. Biochem. Biophys, 267, 787 (1988) 42) B.M. Gesner, V. Ginsburg, Proc. Natl. Acad. Sci., 52, 750 (1964) 43) M.P. Bevilacqua, J J.S. Pober, P.L. Mendrick, R. S. Cotran, M.A. Gimbrone, ibid., 84, 9238 (1978) 44) J.B. Lowe, L.M. Stoolman, R.P. Nair, R.D. Larsen, T.L. Berhend, R.M. Macks, Cell, 63, 475 (1990) 45) M.L. Phillips, E. Nudelman, F.C.A. Gaeta, M. Perez, A.K. Singhal, S. Hakomori, J.C. Paulson, Science, 250, 1130 (1990) 46) J. L. Magnani, Glycobiology, 1, 318 (1991) 47) G. Hart, J. Biol. Chem., 257, 151 (1982) 48) A.V. Muchmore, J.M. Decker, J. Immunol., 138, 2541 (1987) 49) N. Tsuchiya, T. Endo, K. Matsuta, S. Yoshinoya, T. Aikawa, E. Kosuge, F. Takeuchi, T. Miyamo - to, A. Kobata, J. Rheumatol., 16, 285 (1989) 50) F.O. Calvo, R.J. Ryan, Biochemistry., 24, 1953 (1985) 51) J. Arnano, R. Nishimura, S. Sato, A. Kobata, Glycobiology., 1, 45 (1990)

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