Glycosylphosphatidylinositol: Difference between revisions
Content deleted Content added
No edit summary |
m Converted Pfam box into Protein family infobox |
||
| (25 intermediate revisions by 14 users not shown) | |||
| Line 1: | Line 1: | ||
{{short description|Phosphoglyceride attached to proteins}} |
|||
{{Pfam_box |
|||
{{Infobox protein family |
|||
| Symbol = GPI |
| Symbol = GPI |
||
| Name = GPI synthesis components |
| Name = GPI synthesis components |
||
| image = |
| image = |
||
| width = |
| width = |
||
| caption = |
| caption = |
||
| Pfam= |
| Pfam= |
||
| InterPro= |
| InterPro= |
||
| SMART= |
| SMART= |
||
| Prosite = |
| Prosite = |
||
| SCOP = |
| SCOP = |
||
| TCDB = |
| TCDB = |
||
| OPM family= |
| OPM family= |
||
| OPM protein= |
| OPM protein= |
||
| PDB= |
| PDB= |
||
|Membranome superfamily =327 |
|Membranome superfamily =327 |
||
}} |
}} |
||
'''Glycosylphosphatidylinositol''' ({{Audio|GPI_pronunciation.ogg|pronunciation}}) |
'''Glycosylphosphatidylinositol''' ({{Audio|GPI_pronunciation.ogg|pronunciation}}) or '''glycophosphatidylinositol''' ('''GPI''') is a [[phosphoglyceride]] that can be attached to the [[C-terminus]] of a [[protein]] during [[posttranslational modification]]. The resulting [[GPI-anchored protein]]s 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> GPI 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]]. |
||
== Synthesis == |
== Synthesis == |
||
Glycosylated (GPI- |
Glycosylated (GPI-anchored) 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.{{cn|date=September 2022}} |
||
== Cleavage == |
== Cleavage == |
||
[[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 [[ALPI|intestinal]] and [[placental alkaline phosphatase]]s, are known to be GPI-linked and are released by treatment with PLC. GPI-linked proteins are thought to be preferentially located in [[lipid raft]]s, suggesting a high level of organization within plasma membrane microdomains. |
[[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 [[ALPI|intestinal]] and [[placental alkaline phosphatase]]s, are known to be GPI-linked and are released by treatment with PLC. GPI-linked proteins are thought to be preferentially located in [[lipid raft]]s, suggesting a high level of organization within plasma membrane microdomains.{{cn|date=September 2022}} |
||
== GPI-anchor synthesis deficiencies == |
== GPI-anchor synthesis deficiencies == |
||
| Line 30: | Line 31: | ||
=== In humans === |
=== In humans === |
||
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> |
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 | doi-access = free }}</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]]''.{{cn|date=June 2024}} |
||
=== 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 | vauthors = Grab DJ, Verjee Y | |
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 | work = FAO Corporate document depository | publisher = Food and Agricultural Organization of the United Nations | access-date = 2013-07-29 | archive-date = 2018-08-31 | archive-url = https://web.archive.org/web/20180831104205/http://www.fao.org/wairdocs/ilri/x5550e/x5550e0e.htm | url-status = dead }}</ref> |
||
== References == |
== References == |
||
| Line 42: | Line 43: | ||
==External links== |
==External links== |
||
{{Commonscat|Glycosylphosphatidylinositols}} |
{{Commonscat|Glycosylphosphatidylinositols}} |
||
*{{MeshName|Glycosylphosphatidylinositols}} |
* {{MeshName|Glycosylphosphatidylinositols}} |
||
*{{cite web | title = Gpi Anchor Structure | url = http://www.sigmaaldrich.com/life-science/proteomics/post-translational-analysis/glycosylation/structures-symbols/gpi-anchor-structure.html | publisher = Sigma-Aldrich }} |
* {{cite web | title = Gpi Anchor Structure | url = http://www.sigmaaldrich.com/life-science/proteomics/post-translational-analysis/glycosylation/structures-symbols/gpi-anchor-structure.html | publisher = Sigma-Aldrich }} |
||
{{Protein posttranslational modification}} |
{{Protein posttranslational modification}} |
||
| Line 49: | Line 50: | ||
[[Category:Membrane biology]] |
[[Category:Membrane biology]] |
||
[[Category: |
[[Category:Post-translational modification]] |
||
Latest revision as of 16:08, 10 July 2024
| GPI synthesis components | |
|---|---|
| Identifiers | |
| Symbol | GPI |
| Membranome | 327 |
Glycosylphosphatidylinositol () or glycophosphatidylinositol (GPI) is a phosphoglyceride that can be attached to the C-terminus of a protein during posttranslational modification. The resulting GPI-anchored proteins play key roles in a wide variety of biological processes.[1] GPI 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.
Synthesis
[edit]Glycosylated (GPI-anchored) 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.[citation needed]
Cleavage
[edit]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.[citation needed]
GPI-anchor synthesis deficiencies
[edit]In humans
[edit]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.[citation needed]
In other species
[edit]The variable surface glycoproteins from the sleeping sickness protozoan Trypanosoma brucei are attached to the plasma membrane via a GPI anchor.[3]
References
[edit]- ^ 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. Archived from the original on 2018-08-31. Retrieved 2013-07-29.
External links
[edit]
Wikimedia Commons has media related to Glycosylphosphatidylinositols.
- Glycosylphosphatidylinositols at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- "Gpi Anchor Structure". Sigma-Aldrich.