A phosphoethanolamine (Etn-P) moiety can be attached to up to three of the mannoses (Man) of human and yeast GPI precursors during their assembly in the membrane of the endoplasmic reticulum. All the three Etn-Ps originate from phosphatidylethanolamine. Mammals and yeast have a family of three related proteins, of which orthologous mammalian PIG-N and yeast Mcd4 are likely to catalyze transfer of Etn-P to the α1,4-linked Man, PIG-G and yeast Gpi7 are responsible for Etn-P transfer to the α1,6-linked Man, and PIG-O/Gpi13-predominantly in mammals and exclusively in yeast-are involved in Etn-P transfer to the third, α1,2-linked Man. The PIG-G/Gpi7 and PIG-O/Gpi13 proteins are both partnered by the small, hydrophobic PIG-F/Gpi11 protein. The three GPI-Etn-P transferases (Etn-P-T) are large proteins with an N-terminal, lumenally oriented catalytic domain that resembles members of the alkaline phosphatase superfamily, and with multiple transmembrane domains towards their C-termini. The GPI anchors made by Trypanosoma brucei and Plasmodium falciparum bear a single Etn-P on the α1,2-linked Man, and these parasites' genomes encode just one GPI-Etn-P-T. The Etn-P on the α1,2-linked Man becomes amide linked to protein, but the molecular function of the Etn-Ps on the other two Man is unclear, although the severe growth defects of yeast mutants deficient in Mcd4 and Gpi7 indicate that these side branches are of great importance. This chapter focuses on the properties and proposed functions of GPI-Etn-P-T in mammals and yeast, and reviews the phenotypes of yeast GPI-Etn-P-T mutants.
ASJC Scopus subject areas
- Molecular Biology