Glypiation: Difference between revisions
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| ⚫ | '''Glypiation''' is the addition by covalent bonding of a [[glycosylphosphatidylinositol]] (GPI) anchor and is a common [[post-translational modification]] that localizes proteins to cell membranes. This special kind of glycosylation is widely detected on surface glycoproteins in [[eukaryotes]] and some [[Archaea]].<ref>Kobayashi T. et al. (1997) The presence of GPI-linked protein(s) in an archaeobacterium, Sulfolobus acidocaldarius, closely related to eukaryotes. Biochim Biophys Acta. 1334, 1-4.</ref> |
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| ⚫ | '''Glypiation''' is the covalent |
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| ⚫ | Both the lipid moiety of the tail and the sugar residues in the glycan core have considerable variation,<ref>Nosjean O. et al. (1997) Mammalian GPI proteins: Sorting, membrane residence and functions. Biochim Biophys Acta. 1331, 153-86.</ref><ref>Thomas J. R. et al. (1990) Structure, biosynthesis, and function of [[glycosylphosphatidylinositols]]. Biochemistry. 29, 5413-22.</ref><ref>Ikezawa H. (2002) [[Glycosylphosphatidylinositol]] (GPI)-anchored proteins. Biol Pharm Bull. 25, 409-17.</ref><ref>Brewis I. A. et al. (1995) Structures of the glycosyl-phosphatidylinositol anchors of porcine and human renal membrane dipeptidase. Comprehensive structural studies on the porcine anchor and interspecies comparison of the [[glycan]] core structures. J Biol Chem. 270, 22946-56.</ref><ref>Low M. G. (1989) Glycosyl-phosphatidylinositol: A versatile anchor for [[Surface proteins|cell surface proteins]]. FASEB J. 3, 1600-8.</ref><ref>Low M. G. and Saltiel A. R. (1988) Structural and functional roles of glycosyl-phosphatidylinositol in membranes. Science. 239, 268-75.</ref> demonstrating vast functional diversity that includes signal transduction, cell adhesion and immune recognition.<ref>Vainauskas S. and Menon A. K. (2006) Ethanolamine phosphate linked to the first mannose residue of glycosylphosphatidylinositol (GPI) lipids is a major feature of the GPI structure that is recognized by human GPI transamidase. J Biol Chem. 281, 38358-64.</ref> GPI anchors can also be cleaved by enzymes such as phospholipase C to regulate the localization of proteins that are anchored at the plasma membrane. |
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==Mechanism== |
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| ⚫ | Both the lipid moiety of the tail and the sugar residues in the glycan core have considerable variation,<ref>Nosjean O. et al. (1997) Mammalian GPI proteins: Sorting, membrane residence and functions. Biochim Biophys Acta. 1331, 153-86.</ref><ref>Thomas J. R. et al. (1990) Structure, biosynthesis, and function of [[glycosylphosphatidylinositols]]. Biochemistry. 29, 5413-22.</ref><ref>Ikezawa H. (2002) [[Glycosylphosphatidylinositol]] (GPI)-anchored proteins. Biol Pharm Bull. 25, 409-17.</ref><ref>Brewis I. A. et al. (1995) Structures of the glycosyl-phosphatidylinositol anchors of porcine and human renal membrane dipeptidase. Comprehensive structural studies on the porcine anchor and interspecies comparison of the [[glycan]] core structures. J Biol Chem. 270, 22946-56.</ref><ref>Low M. G. (1989) Glycosyl-phosphatidylinositol: A versatile anchor for [[ |
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| ⚫ | Similar to the precursor glycan used for [[N-glycosylation]], GPI anchor biosynthesis begins on the cytoplasmic leaflet of the ER and is completed on the luminal side. During this process, 3-4 Man and various other sugars (e.g., GlcNAc, Gal) are built onto a phosphatidylinositol (PI) molecule embedded in the membrane using sugars donated from sugar nucleotides and dolichol-P-mannose outside and inside the ER, respectively. Additionally, 2-3 phosphoethanolamine (EtN-P) linker residues are donated from [[phosphatidylethanolamine]] in the ER lumen to facilitate binding of the anchor to proteins.<ref>Menon A. K. et al. (1993) Phosphatidylethanolamine is the donor of the terminal phosphoethanolamine group in trypanosome glycosylphosphatidylinositols. EMBO J. 12, 1907-14.</ref><ref>Menon A. K. et al. (1990) Biosynthesis of glycosyl-phosphatidylinositol lipids in Trypanosoma brucei: Involvement of mannosyl-phosphoryldolichol as the mannose donor. EMBO J. 9, 4249-58.</ref><ref>Menon A. K. and Stevens V. L. (1992) Phosphatidylethanolamine is the donor of the ethanolamine residue linking a glycosylphosphatidylinositol anchor to protein. J Biol Chem. 267, 15277-80.</ref><ref>Orlean P. (1990) Dolichol phosphate mannose synthase is required in vivo for glycosyl-phosphatidylinositol membrane anchoring, O mannosylation, and N glycosylation of protein in saccharomyces cerevisiae. Mol Cell Biol. 10, 5796-805.</ref><ref>Imhof I. et al. (2000) Phosphatidylethanolamine is the donor of the phosphorylethanolamine linked to the alpha1,4-linked mannose of yeast GPI structures. Glycobiology. 10, 1271-5.</ref> |
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==Cheeziness== |
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| ⚫ | Similar to the precursor glycan used for [[N-glycosylation]], GPI anchor biosynthesis begins on the cytoplasmic leaflet of the ER and is completed on the luminal side. During this process, 3-4 Man and various other sugars (e.g., GlcNAc, Gal) are built onto a phosphatidylinositol (PI) molecule embedded in the membrane using sugars donated from sugar nucleotides and dolichol-P-mannose outside and inside the ER, respectively. Additionally, 2-3 phosphoethanolamine (EtN-P) linker residues are donated from [[phosphatidylethanolamine]] in the ER lumen to facilitate binding of the anchor to proteins.<ref>Menon A. K. et al. (1993) Phosphatidylethanolamine is the donor of the terminal phosphoethanolamine group in trypanosome glycosylphosphatidylinositols. EMBO J. 12, 1907-14.</ref><ref>Menon A. K. et al. (1990) Biosynthesis of glycosyl-phosphatidylinositol lipids in Trypanosoma brucei: Involvement of mannosyl-phosphoryldolichol as the mannose donor. EMBO J. 9, 4249-58.</ref><ref>Menon A. K. and Stevens V. L. (1992) Phosphatidylethanolamine is the donor of the ethanolamine residue linking a glycosylphosphatidylinositol anchor to protein. J Biol Chem. 267, 15277-80.</ref><ref>Orlean P. (1990) Dolichol phosphate mannose synthase is required in vivo for glycosyl |
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| ⚫ | GPIT does not have a consensus sequence but instead recognizes a C-terminal sequence motif that enables it to covalently attach a GPI anchor to an amino acid in the sequence. This C-terminal sequence is embedded in the ER membrane immediately after translation, and the protein is then cleaved from the sequence and attached to a preformed GPI anchor.<ref name="Kinoshita">Kinoshita T. et al. (1995) Defective glycosyl-phosphatidylinositol anchor synthesis and paroxysmal nocturnal hemoglobinuria. Adv Immunol. 60, 57-103.</ref><ref>Udenfriend S. and Kodukula K. (1995) How glycosylphosphatidylinositol-anchored membrane proteins are made. Annu Rev Biochem. 64, 563-91.</ref> |
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==Prediction of glypiation sites in proteins== |
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''In silico'' prediction of glypiation sites can be performed by: |
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* [http://gpi.unibe.ch/ GPI-SOM: Identification of GPI-anchor signals by a Kohonen Self Organizing Map] |
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* [http://gpcr2.biocomp.unibo.it/predgpi/pred.htm PredGPI: a GPI-anchor predictor] {{Webarchive|url=https://web.archive.org/web/20140813213536/http://gpcr2.biocomp.unibo.it/predgpi/pred.htm |date=2014-08-13 }} |
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| ⚫ | GPIT does not have a consensus sequence but instead recognizes a C-terminal sequence motif that enables it to covalently attach a GPI anchor to an amino acid in the sequence. This C-terminal sequence is embedded in the ER membrane immediately after translation, and the protein is then cleaved from the sequence and attached to a preformed GPI anchor.<ref |
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* [http://mendel.imp.ac.at/sat/gpi/gpi_server.html big-PI Predictor - GPI Modification Site Prediction] {{Webarchive|url=https://web.archive.org/web/20200721214740/http://mendel.imp.ac.at/sat/gpi/gpi_server.html |date=2020-07-21 }} |
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* [https://web.archive.org/web/20121022004341/http://navet.ics.hawaii.edu/~fraganchor/NNHMM/NNHMM.html FragAnchor: GPI-Anchored Protein Prediction Tandem System (NN+HMM)] |
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* [http://www.csbio.sjtu.edu.cn/bioinf/MemType/ MemType-2L] |
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* [https://services.healthtech.dtu.dk/service.php?NetGPI NetGPI] |
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==References== |
==References== |
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{{Reflist}} |
{{Reflist}} |
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[[Category: |
[[Category:Post-translational modification]] |
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Latest revision as of 22:15, 8 June 2024
Glypiation is the addition by covalent bonding of a glycosylphosphatidylinositol (GPI) anchor and is a common post-translational modification that localizes proteins to cell membranes. This special kind of glycosylation is widely detected on surface glycoproteins in eukaryotes and some Archaea.[1]
GPI anchors consist of a phosphoethanolamine linker that binds to the C-terminus of target proteins. Glycan's core structure has a phospholipid tail that anchors the structure to the membrane.
Both the lipid moiety of the tail and the sugar residues in the glycan core have considerable variation,[2][3][4][5][6][7] demonstrating vast functional diversity that includes signal transduction, cell adhesion and immune recognition.[8] GPI anchors can also be cleaved by enzymes such as phospholipase C to regulate the localization of proteins that are anchored at the plasma membrane.
Mechanism
[edit]Similar to the precursor glycan used for N-glycosylation, GPI anchor biosynthesis begins on the cytoplasmic leaflet of the ER and is completed on the luminal side. During this process, 3-4 Man and various other sugars (e.g., GlcNAc, Gal) are built onto a phosphatidylinositol (PI) molecule embedded in the membrane using sugars donated from sugar nucleotides and dolichol-P-mannose outside and inside the ER, respectively. Additionally, 2-3 phosphoethanolamine (EtN-P) linker residues are donated from phosphatidylethanolamine in the ER lumen to facilitate binding of the anchor to proteins.[9][10][11][12][13]
Proteins destined to be glypiated have two signal sequences:
- An N-terminal signal sequence that directs co-translational transport into the ER
- A C-terminal signal sequence that is recognized by a GPI transamidase (GPIT)[8]
GPIT does not have a consensus sequence but instead recognizes a C-terminal sequence motif that enables it to covalently attach a GPI anchor to an amino acid in the sequence. This C-terminal sequence is embedded in the ER membrane immediately after translation, and the protein is then cleaved from the sequence and attached to a preformed GPI anchor.[14][15]
Prediction of glypiation sites in proteins
[edit]In silico prediction of glypiation sites can be performed by:
- GPI-SOM: Identification of GPI-anchor signals by a Kohonen Self Organizing Map
- PredGPI: a GPI-anchor predictor Archived 2014-08-13 at the Wayback Machine
- big-PI Predictor - GPI Modification Site Prediction Archived 2020-07-21 at the Wayback Machine
- FragAnchor: GPI-Anchored Protein Prediction Tandem System (NN+HMM)
- MemType-2L
- NetGPI
References
[edit]- ^ Kobayashi T. et al. (1997) The presence of GPI-linked protein(s) in an archaeobacterium, Sulfolobus acidocaldarius, closely related to eukaryotes. Biochim Biophys Acta. 1334, 1-4.
- ^ Nosjean O. et al. (1997) Mammalian GPI proteins: Sorting, membrane residence and functions. Biochim Biophys Acta. 1331, 153-86.
- ^ Thomas J. R. et al. (1990) Structure, biosynthesis, and function of glycosylphosphatidylinositols. Biochemistry. 29, 5413-22.
- ^ Ikezawa H. (2002) Glycosylphosphatidylinositol (GPI)-anchored proteins. Biol Pharm Bull. 25, 409-17.
- ^ Brewis I. A. et al. (1995) Structures of the glycosyl-phosphatidylinositol anchors of porcine and human renal membrane dipeptidase. Comprehensive structural studies on the porcine anchor and interspecies comparison of the glycan core structures. J Biol Chem. 270, 22946-56.
- ^ Low M. G. (1989) Glycosyl-phosphatidylinositol: A versatile anchor for cell surface proteins. FASEB J. 3, 1600-8.
- ^ Low M. G. and Saltiel A. R. (1988) Structural and functional roles of glycosyl-phosphatidylinositol in membranes. Science. 239, 268-75.
- ^ Vainauskas S. and Menon A. K. (2006) Ethanolamine phosphate linked to the first mannose residue of glycosylphosphatidylinositol (GPI) lipids is a major feature of the GPI structure that is recognized by human GPI transamidase. J Biol Chem. 281, 38358-64.
- ^ Menon A. K. et al. (1993) Phosphatidylethanolamine is the donor of the terminal phosphoethanolamine group in trypanosome glycosylphosphatidylinositols. EMBO J. 12, 1907-14.
- ^ Menon A. K. et al. (1990) Biosynthesis of glycosyl-phosphatidylinositol lipids in Trypanosoma brucei: Involvement of mannosyl-phosphoryldolichol as the mannose donor. EMBO J. 9, 4249-58.
- ^ Menon A. K. and Stevens V. L. (1992) Phosphatidylethanolamine is the donor of the ethanolamine residue linking a glycosylphosphatidylinositol anchor to protein. J Biol Chem. 267, 15277-80.
- ^ Orlean P. (1990) Dolichol phosphate mannose synthase is required in vivo for glycosyl-phosphatidylinositol membrane anchoring, O mannosylation, and N glycosylation of protein in saccharomyces cerevisiae. Mol Cell Biol. 10, 5796-805.
- ^ Imhof I. et al. (2000) Phosphatidylethanolamine is the donor of the phosphorylethanolamine linked to the alpha1,4-linked mannose of yeast GPI structures. Glycobiology. 10, 1271-5.
- ^ Kinoshita T. et al. (1995) Defective glycosyl-phosphatidylinositol anchor synthesis and paroxysmal nocturnal hemoglobinuria. Adv Immunol. 60, 57-103.
- ^ Udenfriend S. and Kodukula K. (1995) How glycosylphosphatidylinositol-anchored membrane proteins are made. Annu Rev Biochem. 64, 563-91.