Glycosylphosphatidylinositol proteins

Udenfriend, S., and Kodukula, K., (1995b). Prediction of omega site in nascent precursor of glycosylphosphatidylinositol protein. Methods Enzymol. 250, 571-582. 

N. Heise, J. Raper, L. U. Buxbaum, T. M. Peranovich, and M. L. de Almeida, Identification of complete precursors for the glycosylphosphatidylinositol protein anchors of Trypanosoma cruzi, J. Biol. Chem., 271 (1996) 16877-16887. 

M. C. Field, A. K. Menon G. A. Cross. A glycosylphosphatidylinositol protein anchor from procyclic stage Trypanosoma brucei lipid structure and biosynthesis. EMBO J, 1991,10, m -111,9. 

R. Amthauer, K. Kodukula, L. Gerber S. Udenfriend. Evidence that the putative COOH-terminal signal transamidase involved in glycosylphosphatidylinositol protein synthesis is present in the endoplasmic reticulum. Proc Natl AcadSci US A, 1993, 90, 3973-3977. 

Much of the plasma membrane cholesterol is removed by incubating cells with P-methylcyclodextrin for several hours. Cells remain viable after this treatment but the raft fraction is reduced and it is inferred that the depleted proteins are normally associated with cholesterol-dependent lipid rafts. Some, but not all, glycosylphosphatidylinositol (GPI)-anchored proteins are recovered in the fractions defined by this procedure. 

A bacterial phosphatidylinositol specific phospholipase C (PI-PLC) had been available for many years before it was demonstrated to strip a number of membrane-bound proteins from eukaryotic cell surfaces [1], Such proteins are anchored by a PI moiety in which the 6 position of inositol is glycosidically linked to glucosamine, which in turn is bonded to a polymannan backbone (Fig. 3-10). The polysaccharide chain is joined to the carboxyl terminal of the anchored protein via amide linkage to ethanolamine phosphate. The presence of a free NH2 group in the glucosamine residue makes the structure labile to nitrous acid. Bacterial PI-PLC hydrolyzes the bond between DAG and phosphati-dylinositols, releasing the water-soluble protein polysac charide-inositol phosphate moiety. These proteins are tethered by glycosylphosphatidylinositol (GPI) anchors. 

Furthermore, according to Howell and Crine (1996), type IV represents multimers of subunits, type V represents proteins that are anchored to the membrane by a covalently linked lipid moiety only, and type VI represents those anchored both by a transmembrane domain and the glycosylphosphatidylinositol (GPI) anchor (see Section III,C,3). 

The last class of three major membrane anchors is caused by the modification by a glycophospholipid, glycosylphosphatidylinositol (GPI) (Udenfriend and Kodukula, 1995a Takeda and Kinoshita, 1995). They are observed in many eukaryotes, especially in protozoa and yeasts. Unlike other classes, the GPI-anchored proteins are exposed at the (extracytoplasmic) surface of the plasma membrane. Thus, we can predict the localization at the plasma membrane from the presence of a GPI anchor, although some of them are further incorporated into the cell wall in S. cerevisiae (as described in Section III,K,1). 

Antony, A. C., and Miller, M. E. (1994). Statistical prediction of the locus of endoproteo-lytic cleavage of the nascent polypeptide in glycosylphosphatidylinositol-anchored proteins. Biochem. J. 298, 9-16. 

Hamada, K., Fukuchi, S., Arisawa, M., Baba, M., and Kitada, K. (1998a). Screening for glycosylphosphatidylinositol (GPI)-dependent cell wall proteins in Saccharomyces cere-visiae. Mol. Gen. Genet. 258, 53-59. 

Molecular targets have been elucidated for Dm-AMPl and Rs-AFP2. Dm-AMPl was found to bind plasma membranes from Neurospora crassa and Saccharomyces cerevisiae in a saturable manner and it competed with closely related defensins for binding. Mutational studies with S. cerevisiae identified lipid raffs containing sphingolipids as a molecular target " while glycosylphosphatidylinositol (GPI)-anchored proteins could be... 

Glycosylphosphatidylinositols (GPI anchors 14) are a class of naturally occu-ring glycophospholipids that do not only bind the C-termini of membrane protein but also mediate signal transduction. Several papers have been devoted to their syntheses. Most of them have a structure related to 14 (with various side-chains that are species-specific) but some yeast GPI have been reported to... 

Scheme 13 Structure of the Natural Protein Membrane Anchor Glycosylphosphatidylinositol...

Specific proteins can be covalently attached via a carbohydrate bridge to membrane-bound PI (glycosylphosphatidylinositol, or GPI). This allows GPI-anchored proteins rapid lateral mobility on the surface of the plasma membrane. A deficiency in the synthesis of GPI in hematopoietic cells results in a hemolytic disease, paroxysmal nocturnal hemoglobinuria. 

Figure 8-13 Structure of glycosylphosphatidylinositol (also called phospha-tidylinositol-glycan) membrane anchors. The core structure is shown in black. The green parts are found in the Thy-1 protein and / or in other anchors.

Anchors, membrane for proteins 402 diphytanylglyceryl 402 glycosylphosphatidylinositol (phosphatidylinositol-glycan) 403, 403s, 523... 

Phosphatidylinositol (PI), a major component of membrane lipids, is formed by displacement of CMP from CMD-dialylglycerol by n/i/o-inositol.186 It is also converted into a variety of less abundant phosphory-lated derivatives that engage in signaling activities (see Fig. 11-9). In addition, PI is a component of the glycosylphosphatidylinositol (GPI) membrane anchors for suface proteins (Fig. 8-13). Free GPI anchors, lacking bound proteins, are also present in membranes. 

Watanabe, R., Funato, K., Venkataraman, K., Futerman, A. H., and Riezman, H. (2002). Sphingolipids are required for the stable membrane association of glycosylphosphatidylinositol-anchored proteins in yeast. J. Biol. Chem. 277(51), 49538—49544. 

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