Glycoproteins are proteins which contain oligosaccharide chains (glycans) covalently 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. Carbohydrates are attached to some proteins to form glycoproteins.
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 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 evidence 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.
There are several types of glycosylation, although the first two are the most common.
Monosaccharides commonly found in eukaryotic glycoproteins include::526
|N-Acetylneuraminic acid||Aminononulosonic acid
The sugar group(s) can assist in protein folding, improve proteins' stability and are involved in cell signalling.
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.
H antigen of the ABO blood compatibility antigens. Other examples of glycoproteins include:
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.
Hormones that are glycoproteins include:
Quoting from recommendations for IUPAC:
A glycoprotein is a compound containing carbohydrate (or glycan) covalently linked to protein. The carbohydrate may be in the form of a monosaccharide, disaccharide(s). oligosaccharide(s), polysaccharide(s), or their derivatives (e.g. sulfo- or phospho-substituted). One, a few, or many carbohydrate units may be present. Proteoglycans are a subclass of glycoproteins in which the carbohydrate units are polysaccharides that contain amino sugars. Such polysaccharides are also known as glycosaminoglycans.
|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.|