Glycosylation - Related Links
Open Access Articles- Top Results for Glycosylation
Modern Chemistry & ApplicationsAdvances in Mass Spectrometry for Glycoscreening and Sequencing in Biomedical Research
Journal of GlycobiologyExploring the Protein Glycosylation Pathways to Find New Therapeutic Alternatives
Journal of GlycobiologyTargeted Shifting of Protein Glycosylation Profiles in Mammalian Cell Culture through Media Supplementation of Cobalt
Current Synthetic and Systems BiologyPromotion of Extracellular Activity of Cellobiohydrolase I from Trichoderma reesei by Protein Glycosylation Engineering in Saccharomyces cerevisiae
Journal of Glycomics & LipidomicsNaturally Occurring Follicle-Stimulating Hormone Glycosylation Variants
Glycosylation (see also chemical glycosylation) is the reaction in which a carbohydrate, i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule (a glycosyl acceptor). In biology glycosylation mainly refers in particular to the enzymatic process that attaches glycans to proteins, lipids, or other organic molecules. This enzymatic process produces one of the fundamental biopolymers found in cells (along with DNA, RNA, and proteins). Glycosylation is a form of co-translational and post-translational modification. Glycans serve a variety of structural and functional roles in membrane and secreted proteins. The majority of proteins synthesized in the rough ER undergo glycosylation. It is an enzyme-directed site-specific process, as opposed to the non-enzymatic chemical reaction of glycation. Glycosylation is also present in the cytoplasm and nucleus as the O-GlcNAc modification. Aglycosylation is a feature of engineered antibodies to bypass glycosylation. Five classes of glycans are produced:
- N-linked glycans attached to a nitrogen of asparagine or arginine side-chains. N-linked glycosylation requires participation of a special lipid called dolichol phosphate.
- O-linked glycans attached to the hydroxyl oxygen of serine, threonine, tyrosine, hydroxylysine, or hydroxyproline side-chains, or to oxygens on lipids such as ceramide
- phospho-glycans linked through the phosphate of a phospho-serine;
- C-linked glycans, a rare form of glycosylation where a sugar is added to a carbon on a tryptophan side-chain
- glypiation, which is the addition of a GPI anchor that links proteins to lipids through glycan linkages.
Glycosylation is the process by which a sugar is covalently attached to a target protein. This modification serves various functions. For instance, some proteins do not fold correctly unless they are glycosylated. In other cases, proteins are not stable unless they contain polysaccharides linked at the amide nitrogen of certain asparagines. Experiments have shown that glycosylation in this case is not a strict requirement for proper folding, but the unglycosylated protein degrades quickly. Glycosylation also plays a role in cell-cell adhesion (a mechanism employed by cells of the immune system) via sugar-binding proteins called lectins, which recognize specific carbohydrate moieties.
Glycosylation increases diversity in the proteome, because almost every aspect of glycosylation can be modified, including:
- Glycosidic bond — the site of glycan linkage
- Glycan composition — the types of sugars that are linked to a given protein
- Glycan structure — can be unbranched or branched chains of sugars
- Glycan length — can be short- or long-chain oligosaccharides
There are various mechanisms for glycosylation, although most share several common features:
- Glycosylation, unlike glycation, is an enzymatic process. Indeed, glycosylation is thought to be the most complex post-translational modification, because of the large number of enzymatic steps involved.
- The donor molecule is often an activated nucleotide sugar
- The process is non-templated (unlike DNA transcription or protein translation); instead, the cell relies on segregating enzymes into different cellular compartments (e.g., endoplasmic reticulum, cisternae in Golgi apparatus). Therefore, glycosylation is a site-specific modification.
Types of glycosylation
N-linked glycosylation is the most common type of glycosidic bond and is important for the folding of some eukaryotic proteins and for cell-cell and cell-extracellular matrix attachment. The N-linked glycosylation process occurs in eukaryotes in the lumen of the endoplasmic reticulum and widely in archaea, but very rarely in bacteria. In addition to their function in protein folding and cellular attachment, the N-liked glycans of a protein can modulate a protein's function, in some cases acting as an on-off switch.
Xylose, fucose, mannose, and GlcNAc phosphoserine glycans have been reported in the literature. Fucose and GlcNAc have been found only in Dictyostelium discoideum, mannose in Leishmania mexicana, and xylose in Trypanosoma cruzi. Mannose has recently been reported in a vertebrate, the mouse, Mus musculus, on the cell-surface laminin receptor alpha dystroglycan4. It has been suggested this rare finding may be linked to the fact that alpha dystroglycan is highly conserved from lower vertebrates to mammals.
A mannose sugar is added to the first tryptophan residue in the sequence W-X-X-W (W indicates tryptophan; X is any amino acid). Thrombospondins are one of the most commonly C-modified proteins, although this form of glycosylation appears elsewhere as well. C-mannosylation is unusual because the sugar is linked to a carbon rather than a reactive atom such as nitrogen or oxygen. Recently, the first crystal structure of a protein containing this type of glycosylation has been determined - that of human complement component 8, PDB ID 3OJY.
Formation of GPI anchors (glypiation)
Over 40 disorders of glycosylation have been reported in humans. These can be divided into four groups: disorders of protein N-glycosylation, disorders of protein O-glycosylation, disorders of lipid glycosylation and disorders of other glycosylation pathways and of multiple glycosylation pathways. No effective treatment is known for any of these disorders. 80% of these affect the nervous system.
- Essentials of Glycobiology. Ajit Varki (ed.) (2nd ed.). Cold Spring Harbor Laboratories Press. ISBN 978-0-87969-770-9.
- Jung ST, Kang TH, Kelton W, Georgiou G (2011). "Bypassing glycosylation: engineering aglycosylated full-length IgG antibodies for human therapy". Curr Opin Biotechnol 22: 858–67. PMID 21420850. doi:10.1016/j.copbio.2011.03.002.
- "Transgenic plants of Nicotiana tabacum L. express aglycosylated monoclonal antibody with antitumor activity". Biotecnologia Aplicada. 2013.
- Drickamer, K; M.E. Taylor (2006). Introduction to Glycobiology (2nd ed.). Oxford University Press, USA. ISBN 978-0-19-928278-4.
- Walsh, Christopher (2006). Posttranslational modification of proteins: Expanding nature's inventory. Roberts and Co. Publishers, Englewood, CO. ISBN 0974707732.
- Maverakis E, Kim K, Shimoda M, Gershwin M, Patel F, Wilken R, Raychaudhuri S, Ruhaak LR, Lebrilla CB (2015). "Glycans in the immune system and The Altered Glycan Theory of Autoimmunity". J Autoimmun 57 (6): 1–13. PMID 25578468. doi:10.1016/j.jaut.2014.12.002.
- William G. Flynne (2008). Biotechnology and Bioengineering. Nova Publishers. pp. 45–. ISBN 978-1-60456-067-1. Retrieved 13 November 2010.
- Yoshida-Moriguchi, T. et al. (2010). Science 327 (5961): 88–92. Missing or empty
- Jaeken, J (2013). "Congenital disorders of glycosylation". Handb Clin Neurol 113: 1737–43. doi:10.1016/B978-0-444-59565-2.00044-7.
- GlycoEP : In silico Platform for Prediction of N-, O- and C-Glycosites in Eukaryotic Protein Sequences PLoS ONE 8(6): e67008
- Online textbook of glycobiology with chapters about glycosylation
- GlyProt: In-silico N-glycosylation of proteins on the web
- NetNGlyc: The NetNglyc server predicts N-glycosylation sites in human proteins using artificial neural networks that examine the sequence context of Asn-Xaa-Ser/Thr sequons.
- Supplementary Material of the Book "The Sugar Code"
- Additional information on glycosylation and figures
- Emanual Maverakis et. al. "Glycans in the immune system and The Altered Glycan Theory of Autoimmunity" (PDF).