Editing Glycoprotein (section)

{{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>