Glycoprotein

N-linked protein glycosylation (N-glycosylation of N-glycans) at Asn residues (Asn-x-Ser/Thr motifs) in glycoproteins.^[1]

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.^[2] 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.^{[citation needed]}

Glycosylation is also known to occur on nucleocytoplasmic proteins in the form of O-GlcNAc.^[3]

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 tyrosine or non-canonical amino acids such as hydroxylysine & hydroxyproline.
• In , sugars are attached to phosphorus on a phosphoserine.
• In , sugars are attached directly to carbon, such as in the addition of mannose to tryptophan.
• In , a beta-GlcNAc is attached to the sulfur atom of a cysteine residue.^[4]
• In glypiation, a GPI glycolipid is attached to the C-terminus of a polypeptide, serving as a membrane anchor.
• In glycation, also known as non-enzymatic glycosylation, sugars are covalently bonded to a protein or lipid molecule, without the controlling action of an enzyme, but through a Maillard reaction.

Monosaccharides[]

Eight sugars commonly found in glycoproteins.

Monosaccharides commonly found in eukaryotic glycoproteins include:^[5]:526

The sugar group(s) can assist in protein folding, improve proteins' stability and are involved in cell signalling.

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.^{[citation needed]} 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.
• sialyl Lewis X antigen on the surface of leukocytes.

H antigen of the ABO blood compatibility antigens. Other examples of glycoproteins include:

• gonadotropins (luteinizing hormone a follicle-stimulating hormone)
• 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.^[7]

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.^[8] 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.^[9][10] 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.^[11]

Hormones[]

Hormones that are glycoproteins include:

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

Distinction between glycoproteins and proteoglycans[]

Quoting from recommendations for IUPAC:^[12]

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.

Functions[]

Analysis[]

A variety of methods used in detection, purification, and structural analysis of glycoproteins are^{[5]:525[13][14]}

See also[]

Notes and references[]

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)
• Emanual Maverakis; et al. "Glycans in the immune system and The Altered Glycan Theory of Autoimmunity" (PDF).
• Biological Importance of the glycosylation of a protein