Glycoprotein

Not to be confused with peptidoglycan, proteoglycan, or glycopeptide.

N-linked protein glycosylation (N-glycosylation of N-glycans) at Asn residues (Asn-x-Ser/Thr motifs) in glycoproteins.

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

Eight sugars commonly found in glycoproteins.

Monosaccharides commonly found in eukaryotic glycoproteins include:

The principal sugars found in human glycoproteins

Sugar	Type	Abbreviation
β-D-Glucose	Hexose	Glc
β-D-Galactose	Hexose	Gal
β-D-Mannose	Hexose	Man
α-L-Fucose	Deoxyhexose	Fuc
N-Acetylgalactosamine	Aminohexose	GalNAc
N-Acetylglucosamine	Aminohexose	GlcNAc
N-Acetylneuraminic acid	Aminononulosonic acid (Sialic acid)	NeuNAc
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 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, 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.
• Glycoprotein-41 (gp41) and glycoprotein-120 (gp120) are HIV viral coat proteins.

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

• 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

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	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

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, 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.

See also

• Ero1
• Female sperm storage
• Glycocalyx
• Glycopeptide
• Gp120
• Gp41
• Miraculin
• P-glycoprotein
• Proteoglycan
• Ribophorin

External links

• Glycan Recognizing Proteins
• 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
• Glycoproteins at the US National Library of Medicine Medical Subject Headings (MeSH)
• Biological Importance of the glycosylation of a protein