Glycoproteins are proteins that contain oligosaccharide chains (glycans) covalently attached to polypeptide side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. Secreted extracellular proteins are often glycosylated. In proteins that have segments extending extracellularly, the extracellular segments are also glycosylated. Glycoproteins are often important integral membrane proteins, where they play a role in cell–cell interactions. Glycoproteins are also formed in the cytosol, but their functions and the pathways producing these modifications in this compartment are less understood.
Types of glycosylation
There are several types of glycosylation, although the first two are the most common.
- In N-glycosylation, sugars are attached to nitrogen, typically on the amide side-chain of asparagine.
- In O-glycosylation, sugars are attached to oxygen, typically on serine or threonine but also on non-canonical amino acids such as hydroxylysine & hydroxyproline.
- In P-glycosylation, sugars are attached to phosphorus on a phosphoserine.
- In C-glycosylation, sugars are attached directly to carbon, such as in the addition of mannose to tryptophan.
- In glypiation, a GPI glycolipid is attached to the C-terminus of a polypeptide, serving as a membrane anchor.
Monosaccharides commonly found in eukaryotic glycoproteins include::526
|N-Acetylneuraminic acid||Aminononulosonic acid
The sugar group(s) can assist in protein folding or improve proteins' stability.
One example of glycoproteins found in the body is mucins, which are secreted in the mucus of the respiratory and digestive tracts. The sugars when attached to mucins give them considerable water-holding capacity and also make them resistant to proteolysis by digestive enzymes.
- molecules such as antibodies (immunoglobulins), which interact directly with antigens.
- molecules of the major histocompatibility complex (or MHC), which are expressed on the surface of cells and interact with T cells as part of the adaptive immune response.
Other examples of glycoproteins include:
- glycoprotein IIb/IIIa, an integrin found on platelets that is required for normal platelet aggregation and adherence to the endothelium.
- components of the zona pellucida, which surrounds the oocyte, and is important for sperm-egg interaction.
- structural glycoproteins, which occur in connective tissue. These help bind together the fibers, cells, and ground substance of connective tissue. They may also help components of the tissue bind to inorganic substances, such as calcium in bone.
- Glycoprotein-41 (gp41) and glycoprotein-120 (gp120) are HIV viral coat proteins.
- Miraculin, is a glycoprotein extracted from Synsepalum dulcificum a berry which alters human tongue receptors to recognize sour foods as sweet.
Variable surface glycoproteins allow the sleeping sickness Trypanosoma parasite to escape the immune response of the host.
Hormones that are glycoproteins include:
- Follicle-stimulating hormone
- Luteinizing hormone
- Thyroid-stimulating hormone
- Human chorionic gonadotropin
- Erythropoietin (EPO)
|Lubricant and protective agent||Mucins|
|Transport molecule||Transferrin, ceruloplasmin|
|Immunologic molecule||Immunoglobulins, histocompatibility antigens|
|Hormone||Human chorionic gonadotropin (HCG), thyroid-stimulating hormone (TSH)|
|Enzyme||Various, e.g., alkaline phosphatase, patatin|
|Cell attachment-recognition site||Various proteins involved in cell–cell (e.g., sperm–oocyte), virus–cell, bacterium–cell, and hormone–cell interactions|
|Antifreeze protein||Certain plasma proteins of coldwater fish|
|Interact with specific carbohydrates||Lectins, selectins (cell adhesion lectins), antibodies|
|Receptor||Various proteins involved in hormone and drug action|
|Affect folding of certain proteins||Calnexin, calreticulin|
|Regulation of development||Notch and its analogs, key proteins in development|
|Hemostasis (and thrombosis)||Specific glycoproteins on the surface membranes of platelets|
|Periodic acid-Schiff stain||Detects glycoproteins as pink bands after electrophoretic separation.|
|Incubation of cultured cells with glycoproteins as radioactive decay bands||Leads to detection of a radioactive sugar after electrophoretic separation.|
|Treatment with appropriate endo- or exoglycosidase or phospholipases||Resultant shifts in electrophoretic migration help distinguish among proteins with N-glycan, O-glycan, or GPI linkages and also between high mannose and complex N-glycans.|
|Agarose-lectin column chromatography, lectin affinity chromatography||To purify glycoproteins or glycopeptides that bind the particular lectin used.|
|Lectin affinity electrophoresis||Resultant shifts in electrophoretic migration help distinguish and characterize glycoforms, i.e. variants of a glycoprotein differing in carbohydrate.|
|Compositional analysis following acid hydrolysis||Identifies sugars that the glycoprotein contains and their stoichiometry.|
|Mass spectrometry||Provides information on molecular mass, composition, sequence, and sometimes branching of a glycan chain. It can also be used for site-specific glycosylation profiling.|
|NMR spectroscopy||To identify specific sugars, their sequence, linkages, and the anomeric nature of glycosidic chain.|
|Multi-angle light scattering||In conjunction with size-exclusion chromatography, UV/Vis absorption and differential refractometry, provides information on molecular mass, protein-carbohydrate ratio, aggregation state, size, and sometimes branching of a glycan chain. In conjunction with composition-gradient analysis, analyzes self- and hetero-association to determine binding affinity and stoichiometry with proteins or carbohydrates in solution without labeling.|
|Dual Polarisation Interferometry||Measures the mechanisms underlying the biomolecular interactions, including reaction rates, affinities and associated conformational changes.|
|Methylation (linkage) analysis||To determine linkage between sugars.|
|Amino acid or cDNA sequencing||Determination of amino acid sequence.|
- Ruddock & Molinari (2006) Journal of Cell Science 119, 4373–4380
- Funakoshi Y, Suzuki T (January 2009). "Glycobiology in the cytosol: The bitter side of a sweet world". Biochim. Biophys. Acta 1790 (2): 81–94. doi:10.1016/j.bbagen.2008.09.009. PMID 18952151.
- Robert K. Murray, Daryl K. Granner & Victor W. Rodwell: "Harper's Illustrated Biochemistry 27th Ed.", McGraw–Hill, 2006
- Glycan classification SIGMA
- Theerasilp S, Kurihara Y (August 1988). "Complete purification and characterization of the taste-modifying protein, miraculin, from miracle fruit". J. Biol. Chem. 263 (23): 11536–9. PMID 3403544.
- 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. doi:10.1016/j.jaut.2014.12.002. PMID 25578468.
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- Glycan Recognizing Proteins
- Structure of Glycoprotein and Carbohydrate Chain – Home Page for Learning Environmental Chemistry
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- Biological Importance of the glycosylation of a protein