:Glycoprotein

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 and 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 S-glycosylation, a beta-GlcNAc is attached to the sulfur atom of a cysteine residue.{{cite journal |vauthors=Stepper J, Shastri S, Loo TS, Preston JC, Novak P, Man P, Moore CH, Havlíček V, Patchett ML, Norris GE |display-authors=6 |title=Cysteine S-glycosylation, a new post-translational modification found in glycopeptide bacteriocins |journal=FEBS Letters |volume=585 |issue=4 |pages=645–650 |date=February 2011 |pmid=21251913 |doi=10.1016/j.febslet.2011.01.023 |s2cid=29992601 |doi-access=}}
• 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.

Image:Glykoproteine Zucker.svg

Monosaccharides commonly found in eukaryotic glycoproteins include:{{cite book |vauthors=Murray RC, Granner DK, Rodwell VW |title=Harper's Illustrated Biochemistry |edition=27th |publisher=McGraw–Hill |date=2006}}{{rp|526}}

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

File:Glycosylation of a polypeptide.png

The critical structural element of all glycoproteins is having oligosaccharides bonded covalently to a protein. There are 10 common monosaccharides in mammalian glycans including: glucose (Glc), fucose (Fuc), xylose (Xyl), mannose (Man), galactose (Gal), N-acetylglucosamine (GlcNAc), glucuronic acid (GlcA), iduronic acid (IdoA), N-acetylgalactosamine (GalNAc), sialic acid, and 5-N-acetylneuraminic acid (Neu5Ac). These glycans link themselves to specific areas of the protein amino acid chain.

The two most common linkages in glycoproteins are N-linked and O-linked glycoproteins. An N-linked glycoprotein has glycan bonds to the nitrogen containing an asparagine amino acid within the protein sequence. An O-linked glycoprotein has the sugar is bonded to an oxygen atom of a serine or threonine amino acid in the protein.

Glycoprotein size and composition can vary largely, with carbohydrate composition ranges from 1% to 70% of the total mass of the glycoprotein. Within the cell, they appear in the blood, the extracellular matrix, or on the outer surface of the plasma membrane, and make up a large portion of the proteins secreted by eukaryotic cells. They are very broad in their applications and can function as a variety of chemicals from antibodies to hormones.

Glycomics is the study of the carbohydrate components of cells. Though not exclusive to glycoproteins, it can reveal more information about different glycoproteins and their structure. One of the purposes of this field of study is to determine which proteins are glycosylated and where in the amino acid sequence the glycosylation occurs. Historically, mass spectrometry has been used to identify the structure of glycoproteins and characterize the carbohydrate chains attached.{{cite journal |vauthors=Dell A, Morris HR |title=Glycoprotein structure determination by mass spectrometry |journal=Science |volume=291 |issue=5512 |pages=2351–2356 |date=March 2001 |pmid=11269315 |doi=10.1126/science.1058890 |bibcode=2001Sci...291.2351D |s2cid=23936441}}

The unique interaction between the oligosaccharide chains have different applications. First, it aids in quality control by identifying misfolded proteins. The oligosaccharide chains also change the solubility and polarity of the proteins that they are bonded to. For example, if the oligosaccharide chains are negatively charged, with enough density around the protein, they can repulse proteolytic enzymes away from the bonded protein. The diversity in interactions lends itself to different types of glycoproteins with different structures and functions.

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|date=December 2007}} 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 and 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.{{cite journal | vauthors = Theerasilp S, Kurihara Y | title = Complete purification and characterization of the taste-modifying protein, miraculin, from miracle fruit | journal = The Journal of Biological Chemistry | volume = 263 | issue = 23 | pages = 11536–11539 | date = August 1988 | doi = 10.1016/S0021-9258(18)37991-2 | pmid = 3403544 | doi-access = free }}

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.{{cite journal |vauthors=Pritchard LK, Vasiljevic S, Ozorowski G, Seabright GE, Cupo A, Ringe R, Kim HJ, Sanders RW, Doores KJ, Burton DR, Wilson IA, Ward AB, Moore JP, Crispin M |display-authors=6 |title=Structural Constraints Determine the Glycosylation of HIV-1 Envelope Trimers |journal=Cell Reports |volume=11 |issue=10 |pages=1604–1613 |date=June 2015 |pmid=26051934 |pmc=4555872 |doi=10.1016/j.celrep.2015.05.017}} 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.{{cite journal |vauthors=Pritchard LK, Spencer DI, Royle L, Bonomelli C, Seabright GE, Behrens AJ, Kulp DW, Menis S, Krumm SA, Dunlop DC, Crispin DJ, Bowden TA, Scanlan CN, Ward AB, Schief WR, Doores KJ, Crispin M |display-authors=6 |title=Glycan clustering stabilizes the mannose patch of HIV-1 and preserves vulnerability to broadly neutralizing antibodies |journal=Nature Communications |volume=6 |pages=7479 |date=June 2015 |pmid=26105115 |pmc=4500839 |doi=10.1038/ncomms8479 |bibcode=2015NatCo...6.7479P}}{{cite journal |vauthors=Behrens AJ, Vasiljevic S, Pritchard LK, Harvey DJ, Andev RS, Krumm SA, Struwe WB, Cupo A, Kumar A, Zitzmann N, Seabright GE, Kramer HB, Spencer DI, Royle L, Lee JH, Klasse PJ, Burton DR, Wilson IA, Ward AB, Sanders RW, Moore JP, Doores KJ, Crispin M |display-authors=6 |title=Composition and Antigenic Effects of Individual Glycan Sites of a Trimeric HIV-1 Envelope Glycoprotein |journal=Cell Reports |volume=14 |issue=11 |pages=2695–2706 |date=March 2016 |pmid=26972002 |pmc=4805854 |doi=10.1016/j.celrep.2016.02.058}} 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.{{cite journal |vauthors=Crispin M, Doores KJ |title=Targeting host-derived glycans on enveloped viruses for antibody-based vaccine design |journal=Current Opinion in Virology |volume=11 |pages=63–69 |date=April 2015 |pmid=25747313 |pmc=4827424 |doi=10.1016/j.coviro.2015.02.002 |series=Viral pathogenesis • Preventive and therapeutic vaccines |author-link2=Katie Doores}}

P-glycoproteins are critical for antitumor research due to its ability block the effects of antitumor drugs.{{cite journal | vauthors = Ambudkar SV, Kimchi-Sarfaty C, Sauna ZE, Gottesman MM | title = P-glycoprotein: from genomics to mechanism | journal = Oncogene | volume = 22 | issue = 47 | pages = 7468–7485 | date = October 2003 | pmid = 14576852 | doi = 10.1038/sj.onc.1206948 | s2cid = 11259597 | doi-access = free }} P-glycoprotein, or multidrug transporter (MDR1), is a type of ABC transporter that transports compounds out of cells. This transportation of compounds out of cells includes drugs made to be delivered to the cell, causing a decrease in drug effectiveness. Therefore, being able to inhibit this behavior would decrease P-glycoprotein interference in drug delivery, making this an important topic in drug discovery. For example, P-Glycoprotein causes a decrease in anti-cancer drug accumulation within tumor cells, limiting the effectiveness of chemotherapies used to treat cancer.

Hormones that are glycoproteins include:

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

{{excerpt|Proteoglycan|Distinction between proteoglycans and glycoproteins}}

A variety of methods used in detection, purification, and structural analysis of glycoproteins are{{rp|525}}

The glycosylation of proteins has an array of different applications from influencing cell to cell communication to changing the thermal stability and the folding of proteins.{{cite journal |vauthors=Davis BG |title=Synthesis of glycoproteins |journal=Chemical Reviews |volume=102 |issue=2 |pages=579–602 |date=February 2002 |pmid=11841255 |doi=10.1021/cr0004310}} Due to the unique abilities of glycoproteins, they can be used in many therapies. By understanding glycoproteins and their synthesis, they can be made to treat cancer, Crohn's Disease, high cholesterol, and more.

The process of glycosylation (binding a carbohydrate to a protein) is a post-translational modification, meaning it happens after the production of the protein. Glycosylation is a process that roughly half of all human proteins undergo and heavily influences the properties and functions of the protein. Within the cell, glycosylation occurs in the endoplasmic reticulum.

File:Variety of glycans.svg

There are several techniques for the assembly of glycoproteins. One technique utilizes recombination. The first consideration for this method is the choice of host, as there are many different factors that can influence the success of glycoprotein recombination such as cost, the host environment, the efficacy of the process, and other considerations. Some examples of host cells include E. coli, yeast, plant cells, insect cells, and mammalian cells. Of these options, mammalian cells are the most common because their use does not face the same challenges that other host cells do such as different glycan structures, shorter half life, and potential unwanted immune responses in humans. Of mammalian cells, the most common cell line used for recombinant glycoprotein production is the Chinese hamster ovary line. However, as technologies develop, the most promising cell lines for recombinant glycoprotein production are human cell lines.

The formation of the link between the glycan and the protein is key element of the synthesis of glycoproteins. The most common method of glycosylation of N-linked glycoproteins is through the reaction between a protected glycan and a protected Asparagine. Similarly, an O-linked glycoprotein can be formed through the addition of a glycosyl donor with a protected Serine or Threonine. These two methods are examples of natural linkage. However, there are also methods of unnatural linkages. Some methods include ligation and a reaction between a serine-derived sulfamidate and thiohexoses in water. Once this linkage is complete, the amino acid sequence can be expanded upon using solid-phase peptide synthesis.

{{div col|colwidth=30em}}

• Ero1
• Female sperm storage
• Glycocalyx
• Glycome
• Glycopeptide
• Gp120
• Gp41
• Miraculin
• P-glycoprotein
• Proteoglycan
• Ribophorin
• Glycan
• Protein
• Monosaccharides

{{div col end}}

{{reflist|refs=

{{cite journal |vauthors=Maverakis E, Kim K, Shimoda M, Gershwin ME, Patel F, Wilken R, Raychaudhuri S, Ruhaak LR, Lebrilla CB |display-authors=6 |title=Glycans in the immune system and The Altered Glycan Theory of Autoimmunity: a critical review |journal=Journal of Autoimmunity |volume=57 |issue=6 |pages=1–13 |date=February 2015 |pmid=25578468 |pmc=4340844 |doi=10.1016/j.jaut.2014.12.002}}

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• {{cite journal |vauthors=Maverakis E, Kim K, Shimoda M, Gershwin ME, Patel F, Wilken R, Raychaudhuri S, Ruhaak LR, Lebrilla CB |title=Glycans in the immune system and The Altered Glycan Theory of Autoimmunity: a critical review |journal=Journal of Autoimmunity |volume=57 |issue= |pages=1–13 |date=February 2015 |pmid=25578468 |pmc=4340844 |doi=10.1016/j.jaut.2014.12.002}}
• {{cite book |vauthors=Berg JM, Tymoczko JL, Stryer L |title=Biochemistry |date=2002 |publisher=W.H. Freeman |location=New York |isbn=978-0-7167-4684-3 |edition=5th |chapter=Carbohydrates Can Be Attached to Proteins to Form Glycoproteins |chapter-url=https://www.ncbi.nlm.nih.gov/books/bv.fcgi?indexed=google&rid=stryer.section.1531}}

{{refend}}

• {{MeshName|Glycoproteins}}
• {{cite web |url=http://www.biochempages.com/2015/08/biological-importance-of-the-glycosylation-of-the-proteins.html |title=Biological Importance of the glycosylation of a protein |work=BiochemPages |date=15 August 2015 |access-date=18 August 2015 |archive-date=30 November 2020 |archive-url=https://web.archive.org/web/20201130225308/https://www.biochempages.com/2015/08/biological-importance-of-the-glycosylation-of-the-proteins.html |url-status=dead }}
• {{cite journal |url=http://www.sciencemag.org/feature/data/carbohydrates.dtl#glycoproteins |archive-url=https://web.archive.org/web/20080109164919/http://www.sciencemag.org/feature/data/carbohydrates.dtl |archive-date=9 January 2008 |title=Carbohydrate Chemistry and Glycobiology: A Web Tour |quote=Special Web Supplement |journal=Science |date=23 March 2001 |volume=291 |issue=5512 |pages=2263–2502}}
• {{cite web |url=http://www.bio-world.com/glycobiology/lectins.html |title=Glycan Recognizing Proteins |work=bioWORLD}}
• {{cite web |url=http://www.ecosci.jp/chem10/weekmol101j_e.html |title=Structure of Glycoprotein and Carbohydrate Chain |work=Home Page for Learning Environmental Chemistry }}

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Category:Carbohydrate chemistry