Glycoproteins are proteins that contain covalently bound oligosaccharides (glycans) which may be N‐ or O‐linked to the protein. The interacting factors controlling glycosylation are complex and include the protein sequence and structure, specificity of relevant glycosyltransferases, availability of donor sugars and other environmental factors. There is therefore, unsurprisingly, great variety in glycosylation, and a single protein may be synthesised in a variety of glycoforms with glycosylation influencing activity and properties of the protein. Glycosylation provides a means of modifying the function of proteins that is not directly dependent on their deoxyribonucleic acid (DNA) template. Some aspects of glycosylation are common to all eukaryotes, but evolution has led to species‐specific features. Glycans function in development, cell–cell recognition, identity, interaction with pathogens and are altered in some diseases such as cancer. 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 post‐translationally, the most frequent modification being glycosylation.
  • Glycosylation may play an important role in protein folding through interaction with the chaperones calnexin and calreticulin.
  • 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.
  • There are many common features in glycosylation in bacteria, parasites, insects, plants and mammals, but also differences. This has implications for the biotechnology industry when recombinant proteins destined for human use are expressed in non‐human cells.
  • In spite of recent advances, glycan analysis remains a complex and specialist field.
  • 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; species‐specific glycosylation; glycan analysis

Figure 1. The monosaccharide linkages to amino acids that form N‐ and O‐linked oligosaccharides. (a) N‐linked d‐GlcNAc β1‐Asn and (b) O‐linked d‐GalNAc α1‐Ser/Thr. The shaded areas show the atoms involved, the nitrogen of asparagine amino groups and the oxygen of serine hydroxyl groups.
Figure 2. (A) 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, the trimannosyl core. This is also conserved in all eukaryotes. (B) 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. Asn, asparagine; GlcNAc, N‐acetylglucosamine; Man, mannose; Gal, galactose; NeuAc, sialic acid; GalNAc, N‐acetylgalactosamine; Ser/Thr, serine/threonine.
Figure 3. The early events in the glycosylation pathway for N‐linked oligosaccharides. ER, endoplasmic reticulum; GA, Golgi apparatus. Black squares, N‐acetylgalactosamine (GalNAc); white circles, mannose (Man); black triangles, glucose (Glc).
Figure 4. The initiation of mucin‐type O‐linked glycosylation and synthesis of core structures 1–4. White squares, N‐acetylgalactosamine (GalNAc); black diamonds, sialic acid (NeuAc); black circles, galactose (Gal); black squares, N‐acetylglucosamine (GlcNAc).
Figure 5. 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.


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Further Reading

Brooks SA, Dwek MV and Schumacher U (2002) Functional and Molecular Glycobiology. Oxford: Bios Scientific. ISBN: 1-859996-022-7.

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.

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. Oxford: Elsevier. ISBN: 978-0-444-52746-2.

von der Lieth CW, Luetteke T and Frank M (eds) (2009) Bioinformatics for Glycobiology and Glycomics: An Introduction (Hardcover). Chichester: Wiley.

Planinc A, Bones J, Dejaegher B, Van Antwerpen P and Delporte C (2016) Glycan characterisation of biopharmaceuticals: updates and perspectives. Analytica Chimica Acta 921: 13–27.

Taniguchi N, Suzuki A, Ito Y, et al. (eds) (2008) Experimental Glycoscience, vol. XVIII. New York: Springer. ISBN: 978-4-431-77921-6.

Taylor ME and Drickamer K (2003) Introduction to Glycobiology, 2nd edn. Oxford: Oxford University Press.

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.

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Brooks, Susan A(Nov 2016) Glycoproteins. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0000705.pub3]