Glycosylphosphatidylinositol: Difference between revisions
No edit summary |
consistent citation formatting |
||
| Line 1: | Line 1: | ||
'''Glycosylphosphatidylinositol''' ({{Audio|GPI_pronunciation.ogg|pronunciation}}), or '''glycophosphatidylinositol''', or '''GPI''' in short, is a [[glycolipid]] that can be attached to the [[C-terminus]] of a [[protein]] during [[posttranslational modification]]. Proteins containing a GPI anchor play key roles in a wide variety of biological processes.<ref>{{ |
'''Glycosylphosphatidylinositol''' ({{Audio|GPI_pronunciation.ogg|pronunciation}}), or '''glycophosphatidylinositol''', or '''GPI''' in short, is a [[glycolipid]] that can be attached to the [[C-terminus]] of a [[protein]] during [[posttranslational modification]]. Proteins containing a GPI anchor play key roles in a wide variety of biological processes.<ref>{{cite journal | vauthors = Paulick MG, Bertozzi CR | title = The glycosylphosphatidylinositol anchor: a complex membrane-anchoring structure for proteins | journal = Biochemistry | volume = 47 | issue = 27 | pages = 6991–7000 | date = July 2008 | pmid = 18557633 | pmc = 2663890 | doi = 10.1021/bi8006324 }}</ref> It is composed of a [[phosphatidylinositol]] group linked through a [[carbohydrate]]-containing linker ([[glucosamine]] and [[mannose]] glycosidically bound to the [[inositol]] residue) and via an [[ethanolamine phosphate]] (EtNP) bridge to the C-terminal amino acid of a mature protein. The two [[fatty acids]] within the hydrophobic phosphatidyl-inositol group anchor the protein to the [[Biological membrane|cell membrane]]. |
||
Glypiated (GPI-linked) proteins contain a [[signal peptide|signal sequence]], thus directing them to the [[endoplasmic reticulum]] (ER). The protein is co-translationally inserted in the ER membrane via a [[translocon]] and is attached to the ER membrane by its hydrophobic C terminus; the majority of the protein extends into the ER lumen. The hydrophobic C-terminal sequence is then cleaved off and replaced by the GPI-anchor. As the protein processes through the [[secretory pathway]], it is transferred via vesicles to the [[Golgi apparatus]] and finally to the plasma membrane where it remains attached to a leaflet of the [[cell membrane]]. Since the [[glypiation]] is the sole means of attachment of such proteins to the membrane, cleavage of the group by [[phospholipase]]s will result in controlled release of the protein from the membrane. The latter mechanism is used ''[[in vitro]]''; i.e. membrane proteins released from membranes in enzymatic assays are glypiated proteins. |
Glypiated (GPI-linked) proteins contain a [[signal peptide|signal sequence]], thus directing them to the [[endoplasmic reticulum]] (ER). The protein is co-translationally inserted in the ER membrane via a [[translocon]] and is attached to the ER membrane by its hydrophobic C terminus; the majority of the protein extends into the ER lumen. The hydrophobic C-terminal sequence is then cleaved off and replaced by the GPI-anchor. As the protein processes through the [[secretory pathway]], it is transferred via vesicles to the [[Golgi apparatus]] and finally to the plasma membrane where it remains attached to a leaflet of the [[cell membrane]]. Since the [[glypiation]] is the sole means of attachment of such proteins to the membrane, cleavage of the group by [[phospholipase]]s will result in controlled release of the protein from the membrane. The latter mechanism is used ''[[in vitro]]''; i.e. membrane proteins released from membranes in enzymatic assays are glypiated proteins. |
||
| Line 23: | Line 23: | ||
|Membranome superfamily =327 |
|Membranome superfamily =327 |
||
}} |
}} |
||
Defects in the GPI-anchor synthesis occur in rare acquired diseases such as [[paroxysmal nocturnal hemoglobinuria]] (PNH) and congenital diseases such as [[hyperphosphatasia with mental retardation syndrome]] (HPMRS). In PNH a somatic defect in blood stem cells, which is required for GPI synthesis, results in faulty GPI linkage of [[decay-accelerating factor]] (DAF) and [[CD59]] in [[red blood cell]]s. The most common cause of PNH are somatic mutations in the X-chromosomal gene [[PIGA]]. However, a PNH case with a germline mutation in the autosomal gene [[PIGT]] and a second acquired somatic hit has also been reported.<ref>{{ |
Defects in the GPI-anchor synthesis occur in rare acquired diseases such as [[paroxysmal nocturnal hemoglobinuria]] (PNH) and congenital diseases such as [[hyperphosphatasia with mental retardation syndrome]] (HPMRS). In PNH a somatic defect in blood stem cells, which is required for GPI synthesis, results in faulty GPI linkage of [[decay-accelerating factor]] (DAF) and [[CD59]] in [[red blood cell]]s. The most common cause of PNH are somatic mutations in the X-chromosomal gene [[PIGA]]. However, a PNH case with a germline mutation in the autosomal gene [[PIGT]] and a second acquired somatic hit has also been reported.<ref>{{cite journal | vauthors = Krawitz PM, Höchsmann B, Murakami Y, Teubner B, Krüger U, Klopocki E, Neitzel H, Hoellein A, Schneider C, Parkhomchuk D, Hecht J, Robinson PN, Mundlos S, Kinoshita T, Schrezenmeier H | title = A case of paroxysmal nocturnal hemoglobinuria caused by a germline mutation and a somatic mutation in PIGT | journal = Blood | volume = 122 | issue = 7 | pages = 1312–5 | date = August 2013 | pmid = 23733340 | doi = 10.1182/blood-2013-01-481499 }}</ref> |
||
Without these proteins linked to the cell surface, the [[complement system]] can [[lysis|lyse]] the cell, and high numbers of RBCs are destroyed, leading to [[hemoglobinuria]]. |
Without these proteins linked to the cell surface, the [[complement system]] can [[lysis|lyse]] the cell, and high numbers of RBCs are destroyed, leading to [[hemoglobinuria]]. |
||
For patients with HPMRS, disease-causing mutations have been reported in the genes PIGV, PIGO, PGAP2 and PGAP3. |
For patients with HPMRS, disease-causing mutations have been reported in the genes PIGV, PIGO, PGAP2 and PGAP3. |
||
== In other species == |
== In other species == |
||
The [[variable surface glycoprotein]]s from the sleeping sickness protozoan ''[[Trypanosoma brucei]]'' are attached to the plasma membrane via a GPI anchor.<ref name="url_FAO">{{cite web | url = http://www.fao.org/wairdocs/ilri/x5550e/x5550e0e.htm | title = Localization of a Variable Surface Glycoprotein Phosphatidylinositol-Specific Phospholipase-C in Trypanosoma brucei brucei | |
The [[variable surface glycoprotein]]s from the sleeping sickness protozoan ''[[Trypanosoma brucei]]'' are attached to the plasma membrane via a GPI anchor.<ref name="url_FAO">{{cite web | url = http://www.fao.org/wairdocs/ilri/x5550e/x5550e0e.htm | title = Localization of a Variable Surface Glycoprotein Phosphatidylinositol-Specific Phospholipase-C in Trypanosoma brucei brucei | vauthors = Grab DJ, Verjee Y | date = | work =FAO Corporate document depository | publisher = Food and Agricultural Organization of the United Nations }}</ref> |
||
== References == |
== References == |
||
| Line 35: | Line 35: | ||
== External links == |
== External links == |
||
* {{MeshName|Glycosylphosphatidylinositols}} |
* {{MeshName|Glycosylphosphatidylinositols}} |
||
| ⚫ | |||
* http:/upwiki/wikibooks/en/thumb/7/7c/GPI-Anchor.jpg/180px-GPI-Anchor.jpg |
|||
| ⚫ | |||
{{Protein posttranslational modification}} |
{{Protein posttranslational modification}} |
||
Revision as of 03:55, 31 August 2018
Glycosylphosphatidylinositol (), or glycophosphatidylinositol, or GPI in short, is a glycolipid that can be attached to the C-terminus of a protein during posttranslational modification. Proteins containing a GPI anchor play key roles in a wide variety of biological processes.[1] It is composed of a phosphatidylinositol group linked through a carbohydrate-containing linker (glucosamine and mannose glycosidically bound to the inositol residue) and via an ethanolamine phosphate (EtNP) bridge to the C-terminal amino acid of a mature protein. The two fatty acids within the hydrophobic phosphatidyl-inositol group anchor the protein to the cell membrane.
Glypiated (GPI-linked) proteins contain a signal sequence, thus directing them to the endoplasmic reticulum (ER). The protein is co-translationally inserted in the ER membrane via a translocon and is attached to the ER membrane by its hydrophobic C terminus; the majority of the protein extends into the ER lumen. The hydrophobic C-terminal sequence is then cleaved off and replaced by the GPI-anchor. As the protein processes through the secretory pathway, it is transferred via vesicles to the Golgi apparatus and finally to the plasma membrane where it remains attached to a leaflet of the cell membrane. Since the glypiation is the sole means of attachment of such proteins to the membrane, cleavage of the group by phospholipases will result in controlled release of the protein from the membrane. The latter mechanism is used in vitro; i.e. membrane proteins released from membranes in enzymatic assays are glypiated proteins.
Phospholipase C (PLC) is an enzyme known to cleave the phospho-glycerol bond found in GPI-anchored proteins. Treatment with PLC will cause release of GPI-linked proteins from the outer cell membrane. The T-cell marker Thy-1 and acetylcholinesterase, as well as both intestinal and placental alkaline phosphatases, are known to be GPI-linked and are released by treatment with PLC. GPI-linked proteins are thought to be preferentially located in lipid rafts, suggesting a high level of organization within plasma membrane microdomains.
GPI-anchor synthesis deficiencies in humans
| GPI synthesis components | |
|---|---|
| Identifiers | |
| Symbol | GPI |
| Membranome | 327 |
Defects in the GPI-anchor synthesis occur in rare acquired diseases such as paroxysmal nocturnal hemoglobinuria (PNH) and congenital diseases such as hyperphosphatasia with mental retardation syndrome (HPMRS). In PNH a somatic defect in blood stem cells, which is required for GPI synthesis, results in faulty GPI linkage of decay-accelerating factor (DAF) and CD59 in red blood cells. The most common cause of PNH are somatic mutations in the X-chromosomal gene PIGA. However, a PNH case with a germline mutation in the autosomal gene PIGT and a second acquired somatic hit has also been reported.[2] Without these proteins linked to the cell surface, the complement system can lyse the cell, and high numbers of RBCs are destroyed, leading to hemoglobinuria. For patients with HPMRS, disease-causing mutations have been reported in the genes PIGV, PIGO, PGAP2 and PGAP3.
In other species
The variable surface glycoproteins from the sleeping sickness protozoan Trypanosoma brucei are attached to the plasma membrane via a GPI anchor.[3]
References
- ^ Paulick MG, Bertozzi CR (July 2008). "The glycosylphosphatidylinositol anchor: a complex membrane-anchoring structure for proteins". Biochemistry. 47 (27): 6991–7000. doi:10.1021/bi8006324. PMC 2663890. PMID 18557633.
- ^ Krawitz PM, Höchsmann B, Murakami Y, Teubner B, Krüger U, Klopocki E, Neitzel H, Hoellein A, Schneider C, Parkhomchuk D, Hecht J, Robinson PN, Mundlos S, Kinoshita T, Schrezenmeier H (August 2013). "A case of paroxysmal nocturnal hemoglobinuria caused by a germline mutation and a somatic mutation in PIGT". Blood. 122 (7): 1312–5. doi:10.1182/blood-2013-01-481499. PMID 23733340.
- ^ Grab DJ, Verjee Y. "Localization of a Variable Surface Glycoprotein Phosphatidylinositol-Specific Phospholipase-C in Trypanosoma brucei brucei". FAO Corporate document depository. Food and Agricultural Organization of the United Nations.
External links
- Glycosylphosphatidylinositols at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- "Gpi Anchor Structure". Sigma-Aldrich.