Editing Glycoprotein

{{short description|Protein with oligosaccharide modifications}}
{{distinguish|peptidoglycan|proteoglycan|glycopeptide}}
{{Use dmy dates|date=April 2017}}
[[Image:Glicoprotein.svg|thumb|right|''N''-linked protein glycosylation (''N''-glycosylation of ''N''-glycans) at [[Asparagine|Asn]] residues (Asn-x-Ser/Thr motifs) in glycoproteins.<ref>{{cite journal |vauthors=Ruddock LW, Molinari M |title=N-glycan processing in ER quality control |journal=Journal of Cell Science |volume=119 |issue=Pt 21 |pages=4373–4380 |date=November 2006 |pmid=17074831 |doi=10.1242/jcs.03225 |doi-access=free}}</ref>]]

'''Glycoproteins''' are [[protein]]s which contain [[oligosaccharide]] (sugar) chains [[Covalent bond|covalently]] attached to [[amino acid]] side-chains. The [[carbohydrate]] is attached to the protein in a [[translation (genetics)|cotranslational]] or [[posttranslational modification]]. This process is known as [[glycosylation]]. [[secretory protein|Secreted extracellular proteins]] are often glycosylated.

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 an additional regulatory mechanism that controls phosphorylation-based signalling.<ref>{{cite journal |vauthors=Funakoshi Y, Suzuki T |title=Glycobiology in the cytosol: the bitter side of a sweet world |journal=Biochimica et Biophysica Acta (BBA) - General Subjects |volume=1790 |issue=2 |pages=81–94 |date=February 2009 |pmid=18952151 |doi=10.1016/j.bbagen.2008.09.009|doi-access=free }}</ref> 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 evidenced 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]].

Though there are different types of glycoproteins, the most common are ''N''-linked and ''O''-linked glycoproteins.<ref name="Picanco_e_Castro_2018">{{cite book |vauthors=Picanco e Castro V, Swiech SH |date=2018 |title=Recombinant Glycoprotein Production Methods and Protocols |publisher=Springer |isbn=978-1-4939-7312-5 |oclc=1005519572}}</ref> These two types of glycoproteins are distinguished by structural differences that give them their names. Glycoproteins vary greatly in composition, making many different compounds such as antibodies or hormones.<ref name="Lehninger_2013">{{cite book |vauthors=Nelson DL, Cox MM, Hoskins AA, Lehninger AL |title=Lehninger Principles of Biochemistry |edition=Sixth |year=2013 |publisher=Macmillan Learning |isbn=978-1-319-38149-3 |oclc=1249676451}}</ref> Due to the wide array of functions within the body, interest in glycoprotein synthesis for medical use has increased.<ref name="Gamblin_2009">{{cite journal |vauthors=Gamblin DP, Scanlan EM, Davis BG |title=Glycoprotein synthesis: an update |journal=Chemical Reviews |volume=109 |issue=1 |pages=131–163 |date=January 2009 |pmid=19093879 |doi=10.1021/cr078291i}}</ref> There are now several methods to synthesize glycoproteins, including recombination and glycosylation of proteins.<ref name="Gamblin_2009" />

Glycosylation is also known to occur on [[Cell nucleus|nucleo]] [[cytoplasm]]ic proteins in the form of [[O-GlcNAc|''O''-GlcNAc]].<ref>{{cite journal |vauthors=Hart GW |title=Three Decades of Research on O-GlcNAcylation - A Major Nutrient Sensor That Regulates Signaling, Transcription and Cellular Metabolism |journal=Frontiers in Endocrinology |volume=5 |pages=183 |date=2014-10-27 |pmid=25386167 |doi=10.3389/fendo.2014.00183 |pmc=4209869 |doi-access=free}}</ref>

==Types of glycosylation==
There are several types of glycosylation, although the first two are the most common.
* In [[N-linked glycosylation|''N''-glycosylation]], sugars are attached to nitrogen, typically on the [[amide]] side-chain of [[asparagine]].
* In [[O-linked glycosylation|''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-linked glycosylation|''P''-glycosylation]], sugars are attached to [[phosphorous acid|phosphorus]] on a [[phosphoserine]].
* In [[C-linked glycosylation|''C''-glycosylation]], sugars are attached directly to carbon, such as in the addition of [[mannose]] to [[tryptophan]].
* In [[S-linked glycosylation|''S''-glycosylation]], a beta-[[GlcNAc]] is attached to the sulfur atom of a [[cysteine]] residue.<ref>{{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=}}</ref>
* In [[glypiation]], a [[Glycophosphatidylinositol|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 ==
[[Image:Glykoproteine Zucker.svg|thumb|Eight sugars commonly found in glycoproteins.]]
Monosaccharides commonly found in eukaryotic glycoproteins include:<ref name="Murray">{{cite book |vauthors=Murray RC, Granner DK, Rodwell VW |title=Harper's Illustrated Biochemistry |edition=27th |publisher=McGraw–Hill |date=2006}}</ref>{{rp|526}}

{| class="wikitable"
|+The principal sugars found in human glycoproteins<ref>[https://www.sigmaaldrich.com/img/assets/15880/glycan_classification.pdf Glycan classification] {{Webarchive|url=https://web.archive.org/web/20121027083417/https://www.sigmaaldrich.com/img/assets/15880/glycan_classification.pdf |date=27 October 2012 }} SIGMA</ref>
|-
! Sugar
! Type
! Abbreviation
|-
| [[Glucose|β-D-Glucose]]
| [[Hexose]]
| Glc
|-
| [[Galactose|β-D-Galactose]]
| Hexose
| Gal
|-
| [[Mannose|β-D-Mannose]]
| Hexose
| Man
|-
| [[Fucose|α-L-Fucose]]
| [[Deoxy sugar|Deoxyhexose]]
| Fuc
|-
| [[N-Acetylgalactosamine]]
| [[Aminosugar|Aminohexose]]
| GalNAc
|-
| [[N-Acetylglucosamine]]
| Aminohexose
| GlcNAc
|-
| [[N-Acetylneuraminic acid]]
| [[neuraminic acid|Aminononulosonic acid]]<br />([[Sialic acid]])
| NeuNAc
|-
| [[Xylose]]
| [[Pentose]]
| Xyl
|-
|}

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

== Structure ==
[[File:Glycosylation of a polypeptide.png|thumb|487x487px|''N''-linked and ''O''-linked glycoproteins]]
The critical structural element of all glycoproteins is having [[oligosaccharide]]s bonded [[Covalent bond|covalently]] to a protein.<ref name="Lehninger_2013" /> There are 10 common monosaccharides in mammalian [[glycan]]s including: [[glucose]] (Glc), [[fucose]] (Fuc), [[xylose]] (Xyl), [[mannose]] (Man), [[galactose]] (Gal), N-[[acetylglucosamine]] (GlcNAc), [[glucuronic acid]] (GlcA), [[iduronic acid]] (IdoA), [[N-Acetylgalactosamine|N-acetylgalactosamine]] (GalNAc), [[sialic acid]], and 5-[[N-Acetylneuraminic acid|N-acetylneuraminic acid]] (Neu5Ac).<ref name="Picanco_e_Castro_2018" /> 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.<ref name="Picanco_e_Castro_2018" /> An ''N''-linked glycoprotein has glycan bonds to the nitrogen containing an [[asparagine]] amino acid within the protein sequence.<ref name="Lehninger_2013" /> An ''O''-linked glycoprotein has the sugar is bonded to an oxygen atom of a [[serine]] or [[threonine]] amino acid in the protein.<ref name="Lehninger_2013" />

Glycoprotein size and composition can vary largely, with carbohydrate composition ranges from 1% to 70% of the total mass of the glycoprotein.<ref name="Lehninger_2013" /> 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.<ref name="Lehninger_2013" /> They are very broad in their applications and can function as a variety of chemicals from antibodies to hormones.<ref name="Lehninger_2013" />

=== Glycomics ===
[[Glycomics]] is the study of the carbohydrate components of cells.<ref name="Lehninger_2013" /> Though not exclusive to glycoproteins, it can reveal more information about different glycoproteins and their structure.<ref name="Lehninger_2013" /> 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.<ref name="Lehninger_2013" /> Historically, mass spectrometry has been used to identify the structure of glycoproteins and characterize the carbohydrate chains attached.<ref name="Lehninger_2013" /><ref name = "Dell_2001">{{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}}</ref>

== Examples ==
The unique interaction between the oligosaccharide chains have different applications. First, it aids in quality control by identifying misfolded proteins.<ref name="Lehninger_2013" /> The oligosaccharide chains also change the solubility and polarity of the proteins that they are bonded to.<ref name="Lehninger_2013" /> 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.<ref name="Lehninger_2013" /> The diversity in interactions lends itself to different types of glycoproteins with different structures and functions.<ref name="Gamblin_2009" />

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.{{Citation needed|date=December 2007}} Examples of glycoproteins in the [[immune system]] are:
* molecules such as [[antibody|antibodies]] (immunoglobulins), which interact directly with [[antigen]]s.
* 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 and 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]]-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.<ref name="jbc-263-23-11536">{{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 }}</ref>

[[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.<ref>{{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}}</ref> 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.<ref>{{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}}</ref><ref>{{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}}</ref> 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.<ref>{{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}}</ref>

[[P-glycoprotein]]s are critical for antitumor research due to its ability block the effects of antitumor drugs.<ref name="Lehninger_2013" /><ref name="Ambudkar_2003">{{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 }}</ref> P-glycoprotein, or multidrug transporter (MDR1), is a type of ABC transporter that transports compounds out of cells.<ref name="Lehninger_2013" /> This transportation of compounds out of cells includes drugs made to be delivered to the cell, causing a decrease in drug effectiveness.<ref name="Lehninger_2013" /> Therefore, being able to inhibit this behavior would decrease P-glycoprotein interference in drug delivery, making this an important topic in drug discovery.<ref name="Lehninger_2013" /> For example, P-Glycoprotein causes a decrease in anti-cancer drug accumulation within tumor cells, limiting the effectiveness of chemotherapies used to treat cancer.<ref name="Ambudkar_2003" />

==Hormones==
[[Hormone]]s that are glycoproteins include:
* [[Follicle-stimulating hormone]]
* [[Luteinizing hormone]]
* [[Thyroid-stimulating hormone]]
* [[Human chorionic gonadotropin]]
* [[Alpha-fetoprotein]]
* [[Erythropoietin|Erythropoietin (EPO)]]

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

==Functions==
{| class="wikitable"
|+ Some functions served by glycoproteins<ref name="Murray" />{{rp|524}}
|-
! Function
! Glycoproteins
|-
| Structural molecule
| [[Collagen]]s
|-
| Lubricant and protective agent
| [[Mucin]]s
|-
| Transport molecule
| [[Transferrin]], [[ceruloplasmin]]
|-
| Immunologic molecule
| [[Antibody|Immunoglobulins]],<ref name="immune_glycan"/> [[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
| [[Lectin]]s, [[selectin]]s (cell adhesion lectins), antibodies
|-
| [[receptor (biochemistry)|Receptor]]
| Various proteins involved in hormone and drug action
|-
| Affect folding of certain proteins
| [[Calnexin]], [[calreticulin]]
|-
| Regulation of development
| [[Notch signaling|Notch]] and its analogs, key proteins in development
|-
| [[Hemostasis]] (and [[thrombosis]])
| Specific glycoproteins on the surface membranes of [[platelet]]s
|-
|}

== Analysis ==
A variety of methods used in detection, purification, and structural analysis of glycoproteins are<ref name="Murray" />{{rp|525}}<ref name="immune_glycan"/><ref name="Dell_2001" />

{| class="wikitable"
|+Some important methods used to study glycoproteins
|-
! Method
! Use
|-
| [[Periodic acid-Schiff stain]]
| Detects glycoproteins as pink bands after [[Electrophoresis|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 [[Endoglycosidase|endo-]] or [[exoglycosidase]] or [[phospholipase]]s
| 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 [[glycoform]]s, 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.<ref name = "immune_glycan"/>

|-
| [[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 change]]s.
|-
| [[Methylation]] (linkage) analysis
| To determine linkage between sugars.
|-
| [[Amino acid]] or [[Complementary DNA|cDNA]] sequencing
| Determination of amino acid sequence.
|-
|}

== Synthesis ==
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.<ref name="Lehninger_2013" /><ref name="Davis_2002">{{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}}</ref> Due to the unique abilities of glycoproteins, they can be used in many therapies.<ref name="Davis_2002" /> By understanding glycoproteins and their synthesis, they can be made to treat cancer, [[Crohn's disease|Crohn's Disease]], high cholesterol, and more.<ref name="Picanco_e_Castro_2018" />

The process of glycosylation (binding a carbohydrate to a protein) is a [[post-translational modification]], meaning it happens after the production of the protein.<ref name="Picanco_e_Castro_2018" /> Glycosylation is a process that roughly half of all human proteins undergo and heavily influences the properties and functions of the protein.<ref name="Picanco_e_Castro_2018" /> Within the cell, glycosylation occurs in the [[endoplasmic reticulum]].<ref name="Picanco_e_Castro_2018" />

=== Recombination ===
[[File:Variety of glycans.svg|thumb|337x337px|Depiction of differences in glycans amongst different animals.]]
There are several techniques for the assembly of glycoproteins. One technique utilizes [[Recombinant DNA|recombination]].<ref name="Picanco_e_Castro_2018" /> 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.<ref name="Picanco_e_Castro_2018" /> Some examples of host cells include E. coli, yeast, plant cells, insect cells, and mammalian cells.<ref name="Picanco_e_Castro_2018" /> 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.<ref name="Picanco_e_Castro_2018" /> Of mammalian cells, the most common cell line used for recombinant glycoprotein production is the [[Chinese hamster ovary cell|Chinese hamster ovary]] line.<ref name="Picanco_e_Castro_2018" /> However, as technologies develop, the most promising cell lines for recombinant glycoprotein production are human cell lines.<ref name="Picanco_e_Castro_2018" />

=== Glycosylation ===
The formation of the link between the glycan and the protein is key element of the synthesis of glycoproteins.<ref name="Gamblin_2009" /> The most common method of glycosylation of N-linked glycoproteins is through the reaction between a protected glycan and a protected Asparagine.<ref name="Gamblin_2009" /> Similarly, an O-linked glycoprotein can be formed through the addition of a [[glycosyl]] donor with a protected [[Serine]] or [[Threonine]].<ref name="Gamblin_2009" /> These two methods are examples of natural linkage.<ref name="Gamblin_2009" /> However, there are also methods of unnatural linkages.<ref name="Gamblin_2009" /> Some methods include ligation and a reaction between a serine-derived sulfamidate and thiohexoses in water.<ref name="Gamblin_2009" /> Once this linkage is complete, the amino acid sequence can be expanded upon using solid-phase peptide synthesis.<ref name="Gamblin_2009" />

== See also ==
{{div col|colwidth=30em}}
* [[ER Oxidoreductin|Ero1]]
* [[Female sperm storage]]
* [[Glycocalyx]]
* [[Glycome]]
* [[Glycopeptide]]
* [[Gp120]]
* [[Gp41]]
* [[Miraculin]]
* [[P-glycoprotein]]
* [[Proteoglycan]]
* [[Ribophorin]]
* [[Glycan]]
* [[Protein]]
* [[Monosaccharides]]
{{div col end}}

== Notes and references ==
{{reflist|refs=
<ref name="immune_glycan">{{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}}</ref>
}}

== Further reading ==
{{refbegin}}
* {{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}}

== External links ==
* {{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:Glycoproteins| ]]
[[Category:Carbohydrate chemistry]]