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The first step of glycosylphosphatidylinositol biosynthesis is mediated by a complex of PIG‐A, PIG‐H, PIG‐C and GPI1
Author(s) -
Watanabe Reika,
Inoue Norimitsu,
Westfall Barbara,
Taron Christopher H.,
Orlean Peter,
Takeda Junji,
Kinoshita Taroh
Publication year - 1998
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/17.4.877
Subject(s) - biology , biosynthesis , guinea pig , biochemistry , microbiology and biotechnology , genetics , enzyme
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 ∼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.