GPI-N-acetylglucosaminyl transferase for the first step of glycosylphosphatidylinositol biosynthesis is mediated by protein complex composed of PIG-A, PIG-H, PIG-C and HGPI 1

R. Watanabe, N. Inoue, B. Westfall, C. H. Taron, P. Orlean, J. Takeda, T. Kinoshita

Research output: Contribution to journalArticlepeer-review

Abstract

Glycosylphosphatidylinositol (GPI) is used as membrane-anchors of many eukaryotic cell-surface proteins. Biosynthesis of GPI is initiated by transfer of N-acetylglucosamine (GlcNAc) from UDP-GIcNAc to phosphatidylinositol (PI). This chemically simple step is genetically complex because three genes were known to be involved in both mammalian and yeast systems. Mammalian PIG-A and PIG-Care homologous to yeast GPI3 and GPI2, respectively, however, mammalian PIG-H is not homologous to yeast GPll. Here we report cloning of a human homologue of GPI1 (hGPI1). HGPI1 cDNA encoded a 581 amino-acid protein that has 24% amino acid identity with yeast Gpilp. We demonstrate that four mammalian gene products, PIG-A, -H, -C and hGPI1 form a protein complex in the endoplasmic reticulum membrane where GPI anchor biosynthesis occurs. The isolated protein complex had GPI-GlcNAc transferase (GPI-GnT) activity in vitro but did not mediate the second reaction. This is consistent with the fact that PIG-L that is involved in the second reaction step did not associate with this complex. Bovine PI was about hundred-fold more efficient substrate than soybean PI. Lyso PI was a very inefficient substrate. These results suggest that GPI-GnT recognizes fatty acyl chains of PI. The unusually complex structure of GPI-GnT suggests that it may have more than a catalytic function.

Original languageEnglish (US)
Pages (from-to)A1084
JournalFASEB Journal
Volume11
Issue number9
StatePublished - Dec 1 1997

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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