Glycoproteins

Tony Merry, University of Manchester, Manchester, UK
Sviatlana Astrautsova, Grodno State Medical University, Grodno, Belarus

Published online: September 2010

DOI: 10.1002/9780470015902.a0000705.pub2

Glycoproteins are proteins that contain covalently bound oligosaccharides (glycans). Although there are structural features of N- and O-linked glycans common to all eukaryotes, species-specific glycosylation reactions create a wide diversity of structures. This is particularly relevant to cell surface glycoproteins although intracellular and even nuclear proteins may be glycosylated. The factors controlling glycosylation are complex and include the protein sequence and structure, specificity of relevant transferase enzymes, availability of donor sugars and other environmental factors. These may all interact so it is not surprising that there is great variety in glycosylation even on the same protein. Glycosylation of proteins is important in such areas as development and interaction with pathogens and provides a means of modifying the function of proteins that is not directly dependent on their deoxyribonucleic acid (DNA) template. Interest in the field is growing and advances in analytical technology now make the field accessible to a wider community.

Key Concepts:

  • Proteins are frequently modified posttranslationally, the most frequent modification being glycosylation.
  • Glycosylation may play an important role in protein folding through interaction with the chaperones calnexin and calreticulin.
  • It has been calculated that as many as 70% of all proteins may be glycosylated.
  • The glycosylation of a protein may vary extensively depending on the cell in which it is produced which may enable the same protein to function in different ways depending where it is expressed.
  • On the cell surface, glycoprotein glycans are frequently involved in cell–cell interactions.
  • Glycosylation of the same protein may change during development or in maturation, for example in cells of the immune system.
  • Glycosylation differs between species even if they are closely related, for example between great apes and man.
  • Analysis of glycosylation has progressed in recent years and is now almost a routine procedure.
  • Particular features of glycosylation may only have functional significance in a particular time and place but can be widely distributed which can make assignment of function to glycan structure difficult.

Keywords: oligosaccharides; N-linked glycosylation; O-linked glycosylation; glycoproteins; posttranslational modifications

Figure 1. The monosaccharide linkages to amino acids that form N- and O-linked oligosaccharides. The shaded areas show the atoms involved, the nitrogen of asparagine amino groups and the oxygen of serine hydroxyl groups. (a) N-linked d-GlcNAc 1-Asn and (b) O-linked d-GalNAc 1-Ser/Thr.
Figure 2. Different types of N-linked oligosaccharide structures: (a) oligomannose type, (b) hybrid type and (c) complex type. The shaded area shows the common feature to all classes of N-links. This is also conserved in all eukaryotes. Asn, asparagine; GlcNAc, N-acetylglucosamine; Man, mannose; Gal, galactose and NeuAc, N-acetylneuraminic acid.
Figure 3. Different types of O-linked oligosaccharide structures. Note that these range in complexity from the simple linear structures to repeating and branched types of structure. (a) Core-1-type O-link found in red blood cells. (b) GlyCAM-1, the core-2 sulfated (* at 6 position of galactose of N-acetylglucosamine) O-linked oligosaccharide from endothelial cells. (c) PSGL-1, the core-2 polylactosamine O-linked oligosaccharide from neutrophils.
Figure 4. Molecular Model of Human erythrocyte CD59 showing three types of glycosylation – N-linked glycans, O-linked glycans and GPI anchor. Molecular dynamics simulation of the possible configurations resulting from the allowed torsion angles calculated for the linkage to the peptide and glycosidic linkages. Model courtesy of Mark Wormald, Oxford Glycobiology Institute.
Figure 5. The early events in the glycosylation pathway for N-linked oligosaccharides. Dol, dolichol lipid; P, phosphate; Glc, glucose; Man, mannose; GlcNAc, N-acetylglucosamine; Glc'ase, glucosidase; Mann'ase, mannosidase and ER, endoplasmic reticulum.
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 References
    Abd Hamid UM, Royle L, Saldova R et al. (2008) A strategy to reveal potential glycan markers from serum glycoproteins associated with breast cancer progression. Glycobiology 18: 1105–1118.
    Apweiler R, Hermjakob H and Sharon N (1999) On the frequency of protein glycosylation, as deduced from analysis of the SWISS-PROT database. Biochimica et Biophysica Acta 1473: 4–8.
    Arnold JN, Wormald MR, Sim RB, Rudd PM and Dwek RA (2007) The impact of glycosylation on the biological function and structure of human immunoglobulins. Annual Review of Immunology 25: 21–50.
    Aryal RP, Ju T and Cummings RD (2010) The endoplasmic reticulum chaperone Cosmc directly promotes in vitro folding of T-synthase. Journal of Biological Chemistry 285: 2456–2462.
    Campbell MP, Royle L, Radcliffe CM, Dwek RA and Rudd PM (2008) GlycoBase and autoGU: tools for HPLC-based glycan analysis. Bioinformatics 24: 1214–1216.
    Ceroni A, Maass K, Geyer H et al. (2008) GlycoWorkbench: a tool for the computer-assisted annotation of mass spectra of glycans. Journal of Proteome Research 7: 1650–1659.
    Chiba Y and Akeboshi H (2009) Glycan engineering and production of ‘humanized’ glycoprotein in yeast cells. Biological & Pharmaceutical Bulletin 32: 786–795.
    Copeland RJ, Bullen JW and Hart GW (2008) Cross-talk between GlcNAcylation and phosphorylation: roles in insulin resistance and glucose toxicity. American Journal of Physiology. Endocrinology and Metabolism 295: E17–E28.
    Davies GJ, Gloster TM and Henrissat B (2005) Recent structural insights into the expanding world of carbohydrate-active enzymes. Current Opinion in Structural Biology 15: 637–645.
    Domann PJ, Pardos-Pardos AC, Fernandes DL et al. (2007) Separation-based glycoprofiling approaches using fluorescent labels. Proteomics 7(suppl. 1): 70–76.
    Elliott S, Lorenzini T, Asher S et al. (2003) Enhancement of therapeutic protein in vivo activities through glycoengineering. Nature Biotechnology 21: 414–421.
    Galili U (2005) The alpha-gal epitope and the anti-Gal antibody in xenotransplantation and in cancer immunotherapy. Immunology and Cell Biology 83: 674–686.
    Gamblin DP, Scanlan EM and Davis BG (2009) Glycoprotein synthesis: an update. Chemical Reviews 109: 131–163.
    Gemmill TR and Trimble RB (1999) Overview of N- and O-linked oligosaccharide structures found in various yeast species. Biochimica et Biophysica Acta 1426(2): 227–237.
    ten Hagen KG, Zhang L, Tian E and Zhang Y (2009) Glycobiology on the fly: developmental and mechanistic insights from Drosophila. Glycobiology 19: 102–111.
    Harvey DJ (2005) Structural determination of N-linked glycans by matrix-assisted laser desorption/ionization and electrospray ionization mass spectrometry. Proteomics 5: 1774–1786.
    Helenius A and Aebi M (2004) Roles of N-linked glycans in the endoplasmic reticulum. Annual Review of Biochemistry 73: 1019–1049.
    Hewitt JE (2009) Abnormal glycosylation of dystroglycan in human genetic disease. Biochimica et Biophysica Acta 1792: 853–861.
    Jefferis R (2007) Antibody therapeutics: isotype and glycoform selection. Expert Opinion on Biological Therapy 7: 1401–1413.
    Jensen PH, Kolarich D and Packer NH (2010) Mucin-type O-glycosylation – putting the pieces together. FEBS Journal 277: 81–94.
    Jimenez-Barbero J, Diaz MD and Nieto PM (2008) NMR structural studies of oligosaccharides related to cancer processes. Anti-Cancer Agents in Medicinal Chemistry 8: 52–63.
    Ju T, Aryal RP, Stowell CJ and Cummings RD (2008) Regulation of protein O-glycosylation by the endoplasmic reticulum-localized molecular chaperone Cosmc. Journal of Cell Biology 182: 531–542.
    Karlsson NG and Thomsson KA (2009) Salivary MUC7 is a major carrier of blood group I type O-linked oligosaccharides serving as the scaffold for sialyl Lewis x. Glycobiology 19: 288–300.
    Mackeen MM, Almond A, Deschamps M et al. (2009) The conformational properties of the Glc3Man unit suggest conformational biasing within the chaperone-assisted glycoprotein folding pathway. Journal of Molecular Biology 387: 335–347.
    North SJ, Hitchen PG, Haslam SM and Dell A (2009) Mass spectrometry in the analysis of N-linked and O-linked glycans. Current Opinion in Structural Biology 19: 498–506.
    Parodi AJ (1999) Reglucosylation of glycoproteins and quality control of glycoprotein folding in the endoplasmic reticulum of yeast cells. Biochimica et Biophysica Acta 1426: 287–295.
    Petrescu A, Wormald MR and Dwek RA (2006) Structural aspects of glycomes with a focus on N-glycosylation and glycoprotein folding. Current Opinion in Structural Biology 16: 600–607.
    Rademacher TW, Parekh RB and Dwek RA (1988) Glycobiology. Annual Review of Biochemistry 57: 785–838.
    Shental-Bechor D and Levy Y (2009) Folding of glycoproteins: toward understanding the biophysics of the glycosylation code. Current Opinion in Structural Biology 19: 524–533.
    Steinberg TH (2009) Protein gel staining methods: an introduction and overview. Methods in Enzymology 463: 541–563.
    Tian E and Ten Hagen KG (2009) Recent insights into the biological roles of mucin-type O-glycosylation. Glycoconjugate Journal 26: 325–334.
    Vadaie N and Jarvis DL (2004) Molecular cloning and functional characterization of a Lepidopteran insect beta4-N-acetylgalactosaminyltransferase with broad substrate specificity, a functional role in glycoprotein biosynthesis, and a potential functional role in glycolipid biosynthesis. Journal of Biological Chemistry 279: 33501–33518.
    Wormald MR, Petrescu AJ, Pao Y et al. (2002) Conformational studies of oligosaccharides and glycopeptides: complementarity of NMR, X-ray crystallography, and molecular modelling. Chemical Reviews 102: 371–386.
    Yan A and Lennarz WJ (2005) Unraveling the mechanism of protein N-glycosylation. Journal of Biological Chemistry 280: 3121–3124.
    Zachara NE and Hart GW (2006) Cell signaling, the essential role of O-GlcNAc!. Biochimica et Biophysica Acta 1761: 599–617.
 Further Reading
    book Fraser-Reid BO, Tatsuta K, Thiem J et al. (eds) (2008) Glycoscience Chemistry and Chemical Biology, 2nd edn, vol. XCVI, 2874 p. Berlin, Heidelberg: Springer. DOI: 10.1007/978-3-540-30429-6; ISBN: 978-3-540-36154-1.
    other Kamerling JP, Boons G-J, Lee YC et al. (eds) (2007) Comprehensive Glycoscience, Volume 3: Biochemistry of Glycoconjugate Glycans; Carbohydrate-Mediated Interactions. Elsevier Science Title ISBN: 978-0-444-52746-2.
    book von der Lieth CW, Luetteke T and Frank M (eds) (2009) Bioinformatics for Glycobiology and Glycomics: An Introduction (Hardcover). Chichester, UK: Wiley.
    other Taniguchi N, Suzuki A, ItoY et al. (eds) (2008) Experimental Glycoscience, XVIII. 978-4-431-77921-6.
    book Taylor ME and Drickamer K (2003) Introduction to Glycobiology, 2nd edn. Oxford: Oxford University Press.
    book Varkii A, Cummings RD, Esko JD et al. (eds) (2009) Essentials of Glycobiology. 2nd edn. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press. ISBN 978-087969770-9.

Related Sub-Topics:

Protein Structure | Posttranslational Modification | Proteins: Structure, Function, Metabolism
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Article Title: Glycoproteins
 
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Merry, Tony, and Astrautsova, Sviatlana(Sep 2010) Glycoproteins. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000705.pub2]