The first step of glycosylphosphatidylinositol biosynthesis is mediated by a complex of PIG-A, PIG-H, PIG-C and GPI1.

Biosynthesis of glycosylphosphatidylinositol (GPI) is initiated by transfer of N-acetylglucosamine (GlcNAc) from UDP-GlcNAc to phosphatidylinositol (PI). This chemically simple step is genetically complex because three genes are required in both mammals and yeast. Mammalian PIG-A and PIG-C are homologous to yeast GPI3 and GPI2, respectively; however, mammalian PIG-H is not ...
homologous to yeast GPI1. Here, we report cloning of a human homolog of GPI1 (hGPI1) and demonstrate that four mammalian gene products form a protein complex in the endoplasmic reticulum membrane. PIG-L, which is involved in the second step in GPI synthesis, GlcNAc-PI de-N-acetylation, did not associate with the isolated complex. The protein complex had GPI-GlcNAc transferase (GPI-GnT) activity in vitro, but did not mediate the second reaction. Bovine PI was utilized approximately 100-fold more efficiently than soybean PI as a substrate, and lyso PI was a very inefficient substrate. These results suggest that GPI-GnT recognizes the fatty acyl chains of PI. The unusually complex organization of GPI-GnT may be relevant to selective usage of PI and/or regulation.
Mesh Terms:
Amino Acid Sequence, Base Sequence, Ceramides, Cloning, Molecular, DNA, Complementary, Enzyme Activation, Glutathione Transferase, Glycosylphosphatidylinositols, Hexosyltransferases, Humans, Macromolecular Substances, Membrane Proteins, Molecular Sequence Data, Phospholipids, Saccharomyces cerevisiae Proteins, Sequence Homology, Amino Acid, Substrate Specificity, Transfection
EMBO J.
Date: Feb. 16, 1998
Download Curated Data For This Publication
8829
Switch View:
  • Interactions 6