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Glycoproteins are which contain oligosaccharide (sugar) chains Covalent bond attached to amino acid 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 often glycosylated. Glycoproteins are also often important integral membrane proteins, where they play a role in cell–cell interactions. It is important to distinguish endoplasmic reticulum-based glycosylation of the secretory system from reversible cytosolic-nuclear glycosylation. Glycoproteins of the cytosol and nucleus can be modified through the reversible addition of a single GlcNAc residue that is considered reciprocal to phosphorylation and the functions of these are likely to be an additional regulatory mechanism that controls phosphorylation-based signalling. In contrast, classical secretory glycosylation can be structurally essential. For example, inhibition of asparagine-linked, i.e. N-linked, glycosylation can prevent proper glycoprotein folding and full inhibition can be toxic to an individual cell. In contrast, perturbation of glycan processing (enzymatic removal/addition of carbohydrate residues to the glycan), which occurs in both the endoplasmic reticulum and Golgi apparatus, is dispensable for isolated cells (as evidenced by survival with glycosides inhibitors) but can lead to human disease (congenital disorders of glycosylation) and can be lethal in animal models. It is therefore likely that the fine processing of glycans is important for endogenous functionality, such as cell trafficking, but that this is likely to have been secondary to its role in host-pathogen interactions. A famous example of this latter effect is the ABO blood group system.
Though there are different types of glycoproteins, the most common are N-linked and O-linked glycoproteins. (2025). 9781493973125, Springer. ISBN 9781493973125 These two types of glycoproteins are distinguished by structural differences that give them their names. Glycoproteins vary greatly in composition, making many different compounds such as antibodies or hormones. (2025). 9781319381493, Macmillan Learning. ISBN 9781319381493 Due to the wide array of functions within the body, interest in glycoprotein synthesis for medical use has increased. There are now several methods to synthesize glycoproteins, including recombination and glycosylation of proteins.
Glycosylation is also known to occur on Cell nucleus proteins in the form of O-GlcNAc.
| +The principal sugars found in human glycoproteins Glycan classification SIGMA | ||
| Glucose | Hexose | Glc |
| Galactose | Hexose | Gal |
| Mannose | Hexose | Man |
| Fucose | Deoxy sugar | Fuc |
| N-Acetylgalactosamine | Aminosugar | GalNAc |
| N-Acetylglucosamine | Aminohexose | GlcNAc |
| N-Acetylneuraminic acid | neuraminic acid (Sialic acid) | NeuNAc |
| Xylose | Pentose | Xyl |
The sugar group(s) can assist in protein folding, improve proteins' stability and are involved in cell signalling.
The two most common linkages in glycoproteins are N-linked and O-linked glycoproteins. An N-linked glycoprotein has glycan bonds to the nitrogen containing an asparagine amino acid within the protein sequence. An O-linked glycoprotein has the sugar is bonded to an oxygen atom of a serine or threonine amino acid in the protein.
Glycoprotein size and composition can vary largely, with carbohydrate composition ranges from 1% to 70% of the total mass of the glycoprotein. Within the cell, they appear in the blood, the extracellular matrix, or on the outer surface of the plasma membrane, and make up a large portion of the proteins secreted by eukaryotic cells. They are very broad in their applications and can function as a variety of chemicals from antibodies to hormones.
One example of glycoproteins found in the body is , 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.
Glycoproteins are important for white blood cell recognition. Examples of glycoproteins in the immune system are:
Variable surface glycoproteins allow the sleeping sickness Trypanosoma parasite to escape the immune response of the host.
The viral spike of the human immunodeficiency virus is heavily glycosylated. Approximately half the mass of the spike is glycosylation and the glycans act to limit antibody recognition as the glycans are assembled by the host cell and so are largely 'self'. Over time, some patients can evolve antibodies to recognise the HIV glycans and almost all so-called 'broadly neutralising antibodies (bnAbs) recognise some glycans. This is possible mainly because the unusually high density of glycans hinders normal glycan maturation and they are therefore trapped in the premature, high-mannose, state. This provides a window for immune recognition. In addition, as these glycans are much less variable than the underlying protein, they have emerged as promising targets for vaccine design.
are critical for antitumor research due to its ability block the effects of antitumor drugs. P-glycoprotein, or multidrug transporter (MDR1), is a type of ABC transporter that transports compounds out of cells. This transportation of compounds out of cells includes drugs made to be delivered to the cell, causing a decrease in drug effectiveness. Therefore, being able to inhibit this behavior would decrease P-glycoprotein interference in drug delivery, making this an important topic in drug discovery. For example, P-Glycoprotein causes a decrease in anti-cancer drug accumulation within tumor cells, limiting the effectiveness of chemotherapies used to treat cancer.
| + Some functions served by glycoproteins | |
| Structural molecule | |
| Lubricant and protective agent | |
| Transport molecule | Transferrin, ceruloplasmin |
| Immunologic molecule | Antibody, 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 | , (cell adhesion lectins), antibodies |
| Receptor | Various proteins involved in hormone and drug action |
| Affect folding of certain proteins | Calnexin, calreticulin |
| Regulation of development | Notch signaling and its analogs, key proteins in development |
| Hemostasis (and thrombosis) | Specific glycoproteins on the surface membranes of |
| +Some important methods used to study glycoproteins | |
| Periodic acid-Schiff stain | Detects glycoproteins as pink bands after Electrophoresis separation. |
| Incubation of cultured cells with glycoproteins as radioactive decay bands | Leads to detection of a radioactive sugar after electrophoretic separation. |
| Treatment with appropriate Endoglycosidase or exoglycosidase or | 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 , 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. |
The process of glycosylation (binding a carbohydrate to a protein) is a post-translational modification, meaning it happens after the production of the protein. Glycosylation is a process that roughly half of all human proteins undergo and heavily influences the properties and functions of the protein. Within the cell, glycosylation occurs in the endoplasmic reticulum.
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