Glycoproteins are protein
s which contain oligosaccharide
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
Glycosylation is also known to occur on nucleocytoplasmic proteins in the form of ''O''-GlcNAc
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
, but also on tyrosine
or non-canonical amino acids such as hydroxylysine
* 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
* In S-glycosylation
, a beta-GlcNAc
is attached to the sulfur atom of a cysteine
* 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
Eight sugars commonly found in glycoproteins.
Monosaccharides commonly found in eukaryotic glycoproteins include:
[Robert K. Murray, Daryl K. Granner & Victor W. Rodwell: "Harper's Illustrated Biochemistry 27th Ed.", McGraw–Hill, 2006]
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 mucin
s, 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
* molecules such as antibodies
(immunoglobulins), which interact directly with antigen
* molecules of the ''major histocompatibility complex
'' (or MHC), which are expressed on the surface of cells and interact with T cell
s 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 platelet
s 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
* 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
* 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
, is a glycoprotein extracted from ''Synsepalum dulcificum
'' a berry
which alters human tongue receptors to recognize sour foods as sweet.
Variable surface glycoprotein
s 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.
s that are glycoproteins include:
* Follicle-stimulating hormone
* Luteinizing hormone
* Thyroid-stimulating hormone
* Human chorionic gonadotropin
* Erythropoietin (EPO)
Distinction between glycoproteins and proteoglycans
Quoting from recommendations for IUPAC:
A variety of methods used in detection, purification, and structural analysis of glycoproteins are
* Female sperm storage
Notes and references
Glycan Recognizing Proteins
– Home Page for Learning Environmental Chemistry
Biochemistry 5thE 11.3. Carbohydrates Can Be Attached to Proteins to Form GlycoproteinsCarbohydrate Chemistry and Glycobiology: A Web Tour
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