Recent developments in the molecular, biochemical and functional characterization of GPI8 and the GPI-anchoring mechanism [Review]

Michele Zacks, Nisha Garg

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Glycoconjugates are utilized by eukaryotic organisms ranging from yeast to humans for the cell surface expression of a wide variety of proteins and lipids. These glycoconjugates are expressed as enzymes or receptors and serve a diversity of functions, including cell signaling and cell survival. In parasitic protozoans, glycoconjugates play roles in infectivity, survival, virulence and immune evasion. Among the alternate glycoconjugate structures that have been identified, glycosylphosphatidylinositols (GPIs) represent a universal structure for the anchorage of proteins, lipids, and phosphosaccharides to cellular membranes. Biosynthesis of the GPI is a multi-step process that culminates in the attachment of the assembled GPI to a precursor protein. This final step in the transfer of the GPI to a protein is catalyzed by GPI8 of the putative transamidase complex (TAM). GPI8 functions dually to perform the proteolytic cleavage of the C-terminal signal sequence of the precursor protein, followed by the formation of an amide bond between the protein and the ethanolamine phosphate of the GPI. This review summarizes the current aggregate of biochemical, gene-disruption and active site mutagenesis studies, which provide evidence that GPI8 is responsible for the protein-GPI anchoring reaction. We describe recently published studies that have identified other potential components of the TAM complex and that have elucidated their likely role in protein-GPI attachment. Further, we discuss the biochemical, molecular and functional differences between protozoan and mammalian GPI8 and the protein-GPI anchoring machinery. Finally, we will present the implications of these studies for the development of anti-parasite drug therapies.

Original languageEnglish (US)
Pages (from-to)209-225
Number of pages17
JournalMolecular Membrane Biology
Volume23
Issue number3
DOIs
StatePublished - May 1 2006

Fingerprint

Glycosylphosphatidylinositols
Glycoconjugates
Proteins
Protein Precursors
Immune Evasion
Lipids
Protein Sorting Signals
Amides
Mutagenesis
Virulence
Catalytic Domain
Cell Survival
Parasites
Yeasts
Drug Therapy
Membranes
Survival
Enzymes

Keywords

  • Glycosylphosphatidylinositol
  • GPI8
  • Protein-GPI anchoring mechanism
  • Transamidase complex

ASJC Scopus subject areas

  • Cell Biology

Cite this

Recent developments in the molecular, biochemical and functional characterization of GPI8 and the GPI-anchoring mechanism [Review]. / Zacks, Michele; Garg, Nisha.

In: Molecular Membrane Biology, Vol. 23, No. 3, 01.05.2006, p. 209-225.

Research output: Contribution to journalArticle

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