Glycosylation and Disease

Abstract

Glycosylation is the process of attachment of carbohydrates (glycans) to proteins and lipids to form the glycoproteins and glycolipids found in eukaryotic organisms. Glycosylation reactions are amongst the most common posttranslational modifications that have been reported on proteins, and they function to alter protein size, stability, charge and antigenicity. Glycosylation plays an important role in cancer, inherited diseases, pathogen–host interactions and immune recognition.

Key Concepts

  • The analysis of glycosylation is more complex than DNA and RNA or protein analysis as glycosylation is a non‐template‐driven event.
  • N‐linked glycosylation commences in the endoplasmic reticulum and is completed in the Golgi apparatus. O‐linked glycosylation commences and is completed in the Golgi apparatus.
  • N‐linked glycosylation occurs on asparagine residues in the consensus sequon Asn‐X‐Ser/Thr. O‐linked glycosylation occurs on serine and threonine residues.
  • Many enzymes are involved in both N‐ and O‐linked glycosylation.
  • Glycans play a role in sperm–egg interactions, the implantation process and embryonic development.
  • Congenital disorders in glycosylation result from autosomally dominant mutations in enzymes involved in glycosylation pathways.
  • Glycosylation of proteins influences their half‐life in the serum.
  • N‐ and O‐linked glycosylation have been reported to be altered in cancer and implicated in all of the steps in the metastatic cascade.

Keywords: glycobiology; biosynthesis; congenital disorders; cancer; autoimmune disease

Figure 1. The monosaccharides found in N‐ and O‐linked glycans in eukaryotes.
Figure 2. The simplified approach to representation of glycans. Square box filled blue: GlcNAc; circle filled green: Man; circle filled yellow: Gal; diamond filled magenta: Neu5Ac.
Figure 3. The main types of N‐linked glycans, high mannose, hybrid and complex. Core structures of O‐linked glycans. Square box filled blue: GlcNAc; square box filled yellow: GalNAc; circle filled green: Man; circle filled yellow: Gal; triangle filled red: Fuc; diamond filled magenta: Neu5Ac.
Figure 4. A schematic diagram showing typical analysis protocols for evaluating protein glycosylation in vitro.
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Dwek, Miriam, and Markiv, Anatoliy(Jun 2018) Glycosylation and Disease. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0002151.pub3]