glycoprotein

glycoprotein, organic compound composed of both a protein and a carbohydrate joined together in covalent chemical linkage. These structures occur in many life forms; they are prevalent and important in mammalian tissues. The attached carbohydrate may have several effects: it may help the protein to fold in the proper geometry, stabilize the protein, affect physical properties such as solubility or viscosity, helps it to orient correctly in a membrane, or make it recognizable to another biochemical or cell (see immunity). Many proteins released by cells to the blood and other fluids are glycoproteins. One set of glycoproteins also carry the blood group determinants. The carbohydrate portion of a glycoprotein is usually a small sugar or no more than 8 to 10 individual monosaccharide units. Combinations of up to seven of the many different sugar molecules known to occur in nature comprise the saccharide portions of mammalian glycoproteins: glucose, glucosamine, galactose, galactosamine, mannose, fucose, and sialic acid (a derivative of glucosamine). The linkage between the oligosaccharide and the protein occurs by formation of a chemical bond to only one of four protein amino acids: asparagine, hydroxylysine, serine, or threonine. Solutions of glycoproteins usually exhibit high viscosity, an observation explaining the highly viscous character of egg white, which is composed largely of the glycoprotein ovalbumin. Salivary mucus contains the glycoprotein called mucin. Among other glycoproteins, one particularly interesting example is isolated from certain antarctic fishes who survive near-freezing water temperatures as a result of freezing-point depression of their blood serum by a globular glycoprotein. This molecule is a remarkably effective freezing point depressant.

Not to be confused with peptidoglycan.

Glycoproteins are proteins that contain oligosaccharide chains (glycans) covalently attached to their polypeptide side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. In proteins that have segments extending extracellularly, the extracellular segments are often glycosylated. Glycoproteins are often important integral membrane proteins, where they play a role in cell-cell interactions.

N-glycosylation and O-glycosylation

There are two types of glycosylation:

• In N-glycosylation (see on the right), the addition of sugar chains can happen at the amide nitrogen on the side chain of the asparagine.
• In O-glycosylation, the addition of sugar chains can happen on the hydroxyl oxygen on the side chain of hydroxylysine, hydroxyproline, serine, or threonine.

Monosaccharides

Monosaccharides commonly found in eukaryotic glycoproteins include:

The principal sugars found in human glycoproteins

Sugar	Type	Abbreviation
Galactose	Hexose	Gal
Glucose	Hexose	Glc
Mannose	Hexose	Man
N-Acetylneuraminic acid	Sialic acid (nine C atoms)	NeuAc
Fucose	Deoxyhexose	Fuc
N-Acetylgalactosamine	Aminohexase	GalNAc
N-Acetylglucosamine	Aminohexase	GlcNAc
Xylose	Pentose	Xyl

The sugar group(s) can assist in protein folding or improve proteins' stability.

Examples

One example of glycoproteins found in the body is mucins, which are secreted in the mucus of the respiratory and digestive tracts. The sugars 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, especially in mammals. Examples of glycoproteins in the immune system are:

• 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.

Soluble glycoproteins often show a high viscosity, for example, in egg white and blood plasma.

Hormones

Hormones that are glycoproteins include:

• Follicle-stimulating hormone
• Luteinizing hormone
• Thyroid-stimulating hormone
• human chorionic gonadotropin
• Alpha-fetoprotein
• Erythropoietin (EPO)

Functions

Some functions served by glycoproteins

Function	Glycoproteins
Structural molecule	Collagens
Lubricant and protective agent	Mucins
Transport molecule	Transferrin, ceruloplasmin
Immunologic molecule	Immunoglobins, histocompatibility antigens
Hormone	Chorionoic gonadotropin, thyroid-stimulating hormone (TSH)
Enzyme	Various, eg, alkaline phosphatase
Cell attachment-recognition site	Various proteins involved in cell-cell (eg, sperm-oocyte), virus-cell, bacterium-cell, and hormone cell interactions
Antifreeze	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

Analysis

A variety of methods used in detection, purification, and structural analysis of glycoproteins are

Some important methods used to study glycoproteins

Method	Use
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	To purify glycoproteins or glycopeptides that bind the particular lectin used.
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.
NMR spectroscopy	To identify specific sugars, their sequence, linkages, and the anomeric nature of glycosidic chain.
Methylation (linkage) analysis	To determine linkage between sugars.
Amino acid or cDNA sequencing	Determination of amino acid sequence.

References

See also

• Proteoglycan
• Glycocalyx
• Gp120
• Gp41

External links

• Structure of Glycoprotein and Carbohydrate Chain - Home Page for Learning Environmental Chemistry
• Biochemistry 5thE 11.3. Carbohydrates Can Be Attached to Proteins to Form Glycoproteins
• Carbohydrate Chemistry and Glycobiology: A Web Tour SPECIAL WEB SUPPLEMENT Science 23 March 2001 Vol 291, Issue 5512, Pages 2263-2502