Glycosyl phosphatidylinositol

FIGURE 9.20 The glycosyl phosphatidylinositol (GPI) moiety is an elaborate lipidanchoring group. Note the core of three mannose residues and a glucosamine. Additional modifications may include fatty acids at the inositol and glycerol —OH groups. 

Adhesion proteins in this group contain an immunoglobulin domain that is composed of 90-100 amino acids arranged in a sandwich of two sheets of antiparallei strands. Some members of this family also contain fibronectin type III—like domains in addition to the immunoglobulin domain. Immunoglobulin-related adhesion proteins either can exist as transmembrane structures or can be attached to cell membranes via glycosyl phosphatidylinositol links (B4, R5). 

Caro, L., Tettelin, H., Vossen, J., Ram, A., van den Ende, H., and Klis, F. (1997). In silico identification of glycosyl-phosphatidylinositol-anchored plasma-membrane and cell wall proteins of Saccharomyces cerevisiae. Yeast 13, 1477—1489. 

PNH is caused by a mutation in certain types of adult blood cells. Because of this mutation, certain types of proteins, including complement inhibitors, are unable to attach to the surface of the cell, as is normally the case. More specifically, the PNH mutation prevents the assembly of a fatty tail, known as a glycosyl-phosphatidylinositol (GPI) anchor, a necessary step in surface attachment of some proteins. 

Albumin, tetanus toxin, autocrine motility factor, interleukin-2, alkaline phosphatase, glycosyl-phosphatidylinositol (GPI)-GFP, polyoma virus, and echo virus 1 (26). 

Type V and Vi proteins carry lipid anchors. These are fatty acids (palmitic acid, myristic acid), isoprenoids (e.g., farnesol), or glycoli-pids such as glycosyl phosphatidylinositol (GPi) that are covalently bound to the peptide chain. 

Figure 4-4. The domain organization of an integral, transmembrane protein as well as the mechanisms for interaction of proteins with membranes. The numbers illustrate the various ways by which proteins can associate with membranes I, multiple transmembrane domains formed of a-helices 2, a pore-forming structure composed of multiple transmembrane domains 3, a transmembrane protein with a single a-helical membrane-spanning domain 4, a protein bound to the membrane by insertion into the bilayer of a covalently attached fatty acid (from the inside) or 5, a glycosyl phosphatidylinositol anchor (from the outside) 6, a protein composed only of an extracellular domain and a membrane-embedded nonpolar tail 7, a peripheral membrane protein noncova-lently bound to an integral membrane protein.

Fig. 2. Lipid-modified proteins, (a) A glycosyl phosphatidylinositol-anchored protein (G, glucosamine M, mannose ...

Many proteins synthesized by the ribosomes of the RER contain short chains of carbohydrates (oligosaccharides) and are called glycoproteins. The oligosaccharides are of two main types O-linked (to the OH side chain of Ser or Thr) and N-linked (to the NH2 side chain of Asn). Some proteins are attached to the plasma membrane by a third type of carbohydrate structure called a glycosyl phosphatidylinositol (GPI) anchor. 

In addition, several proteins are now known to be attached to the plasma membrane via a specific structure that involves carbohydrate, namely a glycosyl phosphatidylinositol (GPI) anchor. This is covered in Topic E2. 

CoQH2 reduced coenzyme Q (ubiquinol) GPI glycosyl phosphatidylinositol... 

Moller LB, Ploug M, Blasi F. Structural requirements for glycosyl-phosphatidylinositol-anchor attachment in the cellular receptor for urokinase plasminogen activator. Eur J Biochem 1992 208(2) 493-500. 

Ploug M, Ronne E, Behrendt N, Jensen AL, Blasi F, Dano K. Cellular receptor for urokinase plasminogen activator. Carboxyl-terminal processing and membrane anchoring by glycosyl-phosphatidylinositol. J Biol Chem 1991 266(3) 1926-1933. 

Low, M.G., 1989, The glycosyl-phosphatidylinositol anchor of membrane proteins. Biochim. Biophys. Acta 988 427 454. 

Stohr, C., Schuler, F., and Tischner, R., 1995, Glycosyl-phosphatidylinositol-anchored proteins exist in the plasma membranes of Chlorella Saccharophila (Kruger) Nadson Plasma-membrane-bound nitrate reductase as an example. Planta 196 284-287. 

Nishihara, M., Utagawa, M., Akutsu, H., and Koga, Y., 1992, Archaea contain a novel diether phosphoglycolipid with a polar head group identical to the conserved core of eucaryal glycosyl phosphatidylinositol. J Biol. Chem. 267 12432-12435. 

AO = Ascorbate oxidase (h)Cp = (human) Ceruloplasmin CT = Charge transfer Hp = Hephaestin GPl = Glycosyl-phosphatidylinositol Lac = Laccase MCO = Multicopper oxidase T1(2,3)D = Type 1 depleted (and/or type 2 or type 3) Tf = Transferrin. 

Cyclic GMP-phosphodiesterase 5 -nitrosoglutathione Gel permeation chromatography G-protein-coupled receptor Glycosyl phosphatidylinositol A Golgi-targeting protein domain... 

Sargiacomo, M., Sudol, M., Tang, Z. and Lisanti, M.P. (1993) Signal transducing molecules and glycosyl-phosphatidylinositol-linked proteins form a caveolin-rich insoluble complex in MDCK cells. J. Cell Biol. 122, im-m. 

Su B, Waneck GL, Flavell RA, Bothwell ALM. The glycosyl phosphatidylinositol anchor is critical for Ly-6A/E-mediated T 63. cell activation. J. Cell. Biol. 1991 112 377-384. 

There are also membrane proteins with extended P-chains through the bilayer, and channel proteins with their hydrophilic inner opening must also contain polar amino acid residues within the lipid bilayer. There is also a group of membrane proteins that are covalently bonded to bilayer lipids, including the glycosyl-phosphatidylinositol anchor [6]. These proteins are exposed on the membrane surface via a spacer arm consisting of an oligoglycan, and specific phospholipases can release the protein. 

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