Biosynthesis of GPI-anchored

T. Kinoshita Enzymes required for biosynthesis of GPI-anchored proteins H. Kunz Synthetic glycopeptides for the development of antitumor vaccines M. A. J. Ferguson GPI and glycoprotein biosynthesis as targets for anti-parasite design... 

Biosynthesis of GPI anchors starts with the core structure assembly by sequential addition of UDP-GlcNAc (followed by iV-deacetylation), dolichol-phosphate-mannose, and phospho-ethanolamine to phosphatidylinositol and culminates in the en bloc transfer to protein shortly after the protein is synthesized. However, the biosynthetic pathways can differ strikingly between different organisms with respect to specific modifications and fatty acid remodeling occurring after completion of the core glycan. This also applies for the point when certain modifications are introduced, e. g. before or after the transfer of the GPI-moiety to the protein. GPI anchors can be cleaved at defined positions by an array of enzymatic and chemical methods, respectively (O Fig. 5). Thus, it becomes possible to identify GPI-anchored proteins and, moreover, analyze the structure and biosynthesis of GPI anchors [103]. 

Evidence that protein addition to GPI anchors occurs in the endoplasmic reticulum stems from kinetic studies on GPI anchor addition to newly synthesized proteins [97,98], the accumulation of unprocessed precursor proteins in the endoplasmic reticulum of yeast and mammalian mutants in GPI anchor biosynthesis [111,112], and the use of a microsomal assay system to analyze the C-terminal processing of GPI-linked proteins [113]. The biosynthesis of GPI anchors also is assumed to be localized to the endoplasmic reticulum. This assumption is well founded since GlcNAc-PI transferase and deacetylase activity co-fractionate with markers for the endoplasmic reticulum [114]. Therefore, at least the initial steps in GPI anchor biosynthesis occur in the endoplasmic reticulum. 

Biosynthesis of GPI-anchored proteins attachment of GPIs to proteins. 53... 

Figure 2. Schematic representation of GPI biosynthetic pathway in Trypanosoma sp. After biosynthesis of GPI anchor it is galactosylated and the VSG/procyclins polypeptide is subsequently added.

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