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Glypiation

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Glypiation is the covalent attachment of a glycosylphosphatidylinositol (GPI) anchor 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 core structure Phospholipid tail that anchors the structure in 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.

Cheeziness

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 2 signal sequences:

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]

References

  1. ^ 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.
  2. ^ Nosjean O. et al. (1997) Mammalian GPI proteins: Sorting, membrane residence and functions. Biochim Biophys Acta. 1331, 153-86.
  3. ^ Thomas J. R. et al. (1990) Structure, biosynthesis, and function of glycosylphosphatidylinositols. Biochemistry. 29, 5413-22.
  4. ^ Ikezawa H. (2002) Glycosylphosphatidylinositol (GPI)-anchored proteins. Biol Pharm Bull. 25, 409-17.
  5. ^ 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.
  6. ^ Low M. G. (1989) Glycosyl-phosphatidylinositol: A versatile anchor for cell surface proteins. FASEB J. 3, 1600-8.
  7. ^ Low M. G. and Saltiel A. R. (1988) Structural and functional roles of glycosyl-phosphatidylinositol in membranes. Science. 239, 268-75.
  8. ^ 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.
  9. ^ Menon A. K. et al. (1993) Phosphatidylethanolamine is the donor of the terminal phosphoethanolamine group in trypanosome glycosylphosphatidylinositols. EMBO J. 12, 1907-14.
  10. ^ 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.
  11. ^ 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.
  12. ^ 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.
  13. ^ 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.
  14. ^ name="Kinoshita">Kinoshita T. et al. (1995) Defective glycosyl phosphatidylinositol anchor synthesis and paroxysmal nocturnal hemoglobinuria. Adv Immunol. 60, 57-103.
  15. ^ Udenfriend S. and Kodukula K. (1995) How glycosylphosphatidylinositol-anchored membrane proteins are made. Annu Rev Biochem. 64, 563-91.
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