The Glycosylphosphatidylinositol Anchor: a Complex Membrane-anchoring Structure for Proteins

Overview

Journal Biochemistry

Specialty Biochemistry

Date 2008 Jun 19

PMID 18557633

Citations 230

Authors

Margot G Paulick

Carolyn R Bertozzi

Affiliations

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Abstract

Positioned at the C-terminus of many eukaryotic proteins, the glycosylphosphatidylinositol (GPI) anchor is a posttranslational modification that anchors the modified protein in the outer leaflet of the cell membrane. The GPI anchor is a complex structure comprising a phosphoethanolamine linker, glycan core, and phospholipid tail. GPI-anchored proteins are structurally and functionally diverse and play vital roles in numerous biological processes. While several GPI-anchored proteins have been characterized, the biological functions of the GPI anchor have yet to be elucidated at a molecular level. This review discusses the structural diversity of the GPI anchor and its putative cellular functions, including involvement in lipid raft partitioning, signal transduction, targeting to the apical membrane, and prion disease pathogenesis. We specifically highlight studies in which chemically synthesized GPI anchors and analogues have been employed to study the roles of this unique posttranslational modification.

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References

Shams-Eldin H, Azzouz N, Niehus S, Smith T, Schwarz R . An efficient method to express GPI-anchor proteins in insect cells. Biochem Biophys Res Commun. 2007; 365(4):657-63. DOI: 10.1016/j.bbrc.2007.11.026. View

Glebov O, Nichols B . Lipid raft proteins have a random distribution during localized activation of the T-cell receptor. Nat Cell Biol. 2004; 6(3):238-43. DOI: 10.1038/ncb1103. View

Grogan M, Kaizuka Y, Conrad R, Groves J, Bertozzi C . Synthesis of lipidated green fluorescent protein and its incorporation in supported lipid bilayers. J Am Chem Soc. 2005; 127(41):14383-7. DOI: 10.1021/ja052407f. View

Kinoshita T, Inoue N . Dissecting and manipulating the pathway for glycosylphos-phatidylinositol-anchor biosynthesis. Curr Opin Chem Biol. 2000; 4(6):632-8. DOI: 10.1016/s1367-5931(00)00151-4. View

Lehto M, Sharom F . Proximity of the protein moiety of a GPI-anchored protein to the membrane surface: a FRET study. Biochemistry. 2002; 41(26):8368-76. DOI: 10.1021/bi012038+. View

Olschewski D, Seidel R, Miesbauer M, Rambold A, Oesterhelt D, Winklhofer K . Semisynthetic murine prion protein equipped with a GPI anchor mimic incorporates into cellular membranes. Chem Biol. 2007; 14(9):994-1006. DOI: 10.1016/j.chembiol.2007.08.007. View

McHugh R, Nagarajan S, Wang Y, Sell K, Selvaraj P . Protein transfer of glycosyl-phosphatidylinositol-B7-1 into tumor cell membranes: a novel approach to tumor immunotherapy. Cancer Res. 1999; 59(10):2433-7. View

Fontaine T, Magnin T, Melhert A, Lamont D, Latge J, Ferguson M . Structures of the glycosylphosphatidylinositol membrane anchors from Aspergillus fumigatus membrane proteins. Glycobiology. 2003; 13(3):169-77. DOI: 10.1093/glycob/cwg004. View

Breydo L, Sun Y, Makarava N, Lee C, Novitskaia V, Bocharova O . Nonpolar substitution at the C-terminus of the prion protein, a mimic of the glycosylphosphatidylinositol anchor, partially impairs amyloid fibril formation. Biochemistry. 2007; 46(3):852-61. PMC: 2522369. DOI: 10.1021/bi061923v. View

10.

Gordon V, Nelson K, Buckley J, Stevens V, Tweten R, Elwood P . Clostridium septicum alpha toxin uses glycosylphosphatidylinositol-anchored protein receptors. J Biol Chem. 1999; 274(38):27274-80. DOI: 10.1074/jbc.274.38.27274. View

11.

Ikezawa H . Glycosylphosphatidylinositol (GPI)-anchored proteins. Biol Pharm Bull. 2002; 25(4):409-17. DOI: 10.1248/bpb.25.409. View

12.

Fukushima K, Ikehara Y, Kanai M, Kochibe N, Kuroki M, Yamashita K . A beta-N-acetylglucosaminyl phosphate diester residue is attached to the glycosylphosphatidylinositol anchor of human placental alkaline phosphatase: a target of the channel-forming toxin aerolysin. J Biol Chem. 2003; 278(38):36296-303. DOI: 10.1074/jbc.M304341200. View

13.

Homans S, Edge C, Ferguson M, Dwek R, Rademacher T . Solution structure of the glycosylphosphatidylinositol membrane anchor glycan of Trypanosoma brucei variant surface glycoprotein. Biochemistry. 1989; 28(7):2881-7. DOI: 10.1021/bi00433a020. View

14.

Oxley D, Bacic A . Structure of the glycosylphosphatidylinositol anchor of an arabinogalactan protein from Pyrus communis suspension-cultured cells. Proc Natl Acad Sci U S A. 1999; 96(25):14246-51. PMC: 24422. DOI: 10.1073/pnas.96.25.14246. View

15.

Ferguson M . The structure, biosynthesis and functions of glycosylphosphatidylinositol anchors, and the contributions of trypanosome research. J Cell Sci. 1999; 112 ( Pt 17):2799-809. DOI: 10.1242/jcs.112.17.2799. View

16.

Paladino S, Sarnataro D, Pillich R, Tivodar S, Nitsch L, Zurzolo C . Protein oligomerization modulates raft partitioning and apical sorting of GPI-anchored proteins. J Cell Biol. 2004; 167(4):699-709. PMC: 2172584. DOI: 10.1083/jcb.200407094. View

17.

BARBONI E, Rivero B, George A, Martin S, Renoup D, Hounsell E . The glycophosphatidylinositol anchor affects the conformation of Thy-1 protein. J Cell Sci. 1995; 108 ( Pt 2):487-97. DOI: 10.1242/jcs.108.2.487. View

18.

Rademacher T, Edge C, Dwek R . Dropping anchor with the lipophosphoglycans. Curr Biol. 1991; 1(1):41-2. DOI: 10.1016/0960-9822(91)90123-e. View

19.

Nakano Y, Noda K, Endo T, Kobata A, Tomita M . Structural study on the glycosyl-phosphatidylinositol anchor and the asparagine-linked sugar chain of a soluble form of CD59 in human urine. Arch Biochem Biophys. 1994; 311(1):117-26. DOI: 10.1006/abbi.1994.1216. View

20.

Tiede A, Bastisch I, Schubert J, Orlean P, Schmidt R . Biosynthesis of glycosylphosphatidylinositols in mammals and unicellular microbes. Biol Chem. 1999; 380(5):503-23. DOI: 10.1515/BC.1999.066. View