Proteins glycosylphosphatidylinositol anchor

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. 

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. 

Udenfriend, S., and Kodukula, K. (1995a). How glycosylphosphatidylinositol-anchored membrane proteins are made. Annu. Rev. Biochem. 64, 563—591. 

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

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. 

Gillmor, C. S., Lukowitz, W., Brininstool, G., Sedbrook, J. C., Hamann, T., et al., Glycosylphosphatidylinositol-anchored proteins are required for cell wall synthesis and morphogenesis in arabidopsis. Plant Cell 2005, 17 (4), 1128-1140. 

Low, M.G., 2000, Glycosylphosphatidylinositol-anchored proteins and their phospholipases. In Cockcroft, S. (ed.), Frontiers in Molecular Biology, Vol. 27, Biology of Phosphoinositides. Oxford University Press, New York, pp. 211-238. 

Sharom, F.J., and Lehto, M.T., 2002, Glycosylphosphatidylinositol-anchored proteins Structure, function, and cleavage by phosphatidylinositol-specific phospholipase C. Biochem. Cell. Biol. 80 535-549. 

Fig. 3.10 A protein anchored to the membrane with a glycosylphosphatidylinositol anchor.

Examples of receptors and ligands involved in RME. Specific gene symbols of representative human receptor and ligand proteins are listed in parentheses. TM transmembrane protein GPI glycosylphosphatidylinositol anchored protein 7TM Seven-transmembrane protein. 

Peyron P, Bordier C, N Diaye EN et al. Nonopsonic phagocytosis of Mycobacterium kansasii by human neutrophils depends on cholesterol and is mediated by CR3 associated with glycosylphosphatidylinositol-anchored proteins.) Immunol 2000 165(9) 5186-5191. 

In the plasma membrane, GSLs are believed to segregate into microdomains that are also enriched in glycosylphosphatidylinositol-anchored proteins, sphingomyelin, and cholesterol [12]. Because of their specific localization on the plasma membrane, especially in... 

S. Undenfriend and K. Kodukula, How glycosylphosphatidylinositol-anchored membrane proteins are... 

Schroeder RJ, Ahmed SN, Zhu Y, London E, Brown DA. Cholesterol and sphingolipid enhance the Triton X-100 insolubility of glycosylphosphatidylinositol-anchored proteins by promoting the formation of detergent-insoluble ordered membrane domains. J Biol Chem 1998 273 1150-1157. 

Kiachopoulos S, Bracher A, Winklhofer KF, Tatzelt J (2005) Pathogenic mutations located in the hydrophobic core of the prion protein interfere with folding and attachment of the glycosylphosphatidylinositol anchor. J Biol Chem 280 9320... 

Becker CF, Liu X, Olschewski D, Castelli R, Seidel R, Seeberger PH (2008) Semisynthesis of a glycosylphosphatidylinositol-anchored prion protein. Angew Chem Int Ed Engl 47 8215-8219... 

Gaynor, E. C., Mondesert, G., Grimme, S.J., Reed, S. I., Orlean, P., and Emr, S. D. (1999). MCD4 encodes a conserved endoplasmic reticulum membrane protein essential for glycosylphosphatidylinositol anchor synthesis in yeast. Mol. Biol. CeU 10, 627-648. 

Atomic force microscopy reveais sphyingomyeiin rafts (orange) protruding from a dioieoyiphosphatidylcholine background (biack) in a mica-supported iipid bilayer. Placental alkaline phosphatase (yellow peaks), a glycosylphosphatidylinositol-anchored protein, is shown to be almost exclusively raft associated. [From D. E. Saslowsky etal., 2002, J. Biot. Chem. 277 26966-26970.1... 

Mammalian PLDs are now the subject of intense interest as they appear to be intimately involved in signal transduction (M. McDermott, 2004 G.M. Jenkins, 2005). Two mammalian PLDs have been identified and these contain several domains often associated with signal transduction proteins including a PH domain and a separate phosphatidylinositol-bis-phosphate-binding domain. PLC and PLD that act on glycosylphosphatidylinositol-anchored proteins on the cell surface are of growing importance and are discussed in Chapter 2. 

Fig. 4. Model showing the interactions between the endothelial cell surface, triacylglycerol-rich lipoproteins, apo C2, and lipoprotein lipase (LPL). Two LPL molecules are shown reacting with the same VLDL particle. These are representative of the multiple LPLs that probably react with each triacylglycerol-rich lipoprotein. The location of the recently identified glycosylphosphatidylinositol-anchored HDL binding protein-1 within the substrate-lipase complex has not yet been identified.

The four major types of protein lipidation are A-myristoylation, palmitoylation, prenylation and glycosylphosphatidylinositol-anchor (GPI-anchor) addition (Table 1). 

Walton, K. A., Hsieh, X., Gharavi, N., Wang, S., Wang, G., Yeh, M., Cole, A. L., and Berliner, J. A. 2003b. Receptors involved in the oxidized l-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine-mediated synthesis of interleukin-8. A role for Toll-like receptor 4 and a glycosylphosphatidylinositol-anchored protein. 278, 29661-6. 

Berliner, J. A., Receptors involved in the oxidized l-palmitoyl-2-arachidonoyl-sw-glycero-3-phosphorylcholine-mediated synthesis of interleukin-8. A role for Toll-like receptor 4 and a glycosylphosphatidylinositol-anchored protein, 2003,... 

Ascidian sperm glycosylphosphatidylinositol-anchored CRISP-like protein as a binding partner for an allorecognizable sperm receptor on the vitelline coat. J Biol Chem 283(31) 21725-21733. 

---