The initial enzyme for glycosylphosphatidylinositol biosynthesis requires PIG-Y, a seventh component

The initial enzyme for glycosylphosphatidylinositol biosynthesis requires PIG-Y, a seventh component
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DOI:
10.1091/mbc.e05-08-0743
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发表时间:
2005-11-01
影响因子:
3.3
通讯作者:
Kinoshita, T
Kinoshita, T
中科院分区:
生物学3区
文献类型:
--
作者:
Murakami, Y;Siripanyaphinyo, U;Kinoshita, T

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糖基磷脂酰肌醇 (GPI) 的生物合成是由一种异常复杂的 GPI-N-乙酰氨基葡萄糖转移酶 (GPI-GnT) 启动的,该酶由至少六种蛋白质组成。在这里,我们报告人类 GPI-GnT 需要另一种成分,称为 PIG-Y,一种具有两个跨膜结构域的 71 个氨基酸的蛋白质。 Burkitt 淋巴瘤细胞系 Daudi 在 GPI 锚定蛋白的表面表达方面存在严重缺陷,是 PIG-Y 的无效突变体。在没有 PIG-Y 的情况下形成了六种成分的复合物。 PIG-Y 似乎与 PIG-A 直接相关,这意味着 PIG-Y 是通过直接与催化亚基 PIG-A 结合来调节 GPI-GnT 活性的关键分子。 PIG-Y 可能与酵母 Eri1p 同源,Eri1p 是 GPI-GnT 的一个组成部分。我们没有获得哺乳动物细胞中 GPI-GnT 和 ras GTPases 之间功能联系的证据,正如酵母细胞所报道的那样。单个转录本编码 PIG-Y,并且在其 5' 侧编码另一种蛋白质 PreY,该蛋白质在多种生物体中具有同源物,其特征在于称为 DUF343 的保守结构域。这两种蛋白质是通过 PreY 起始位点的渗漏扫描从一种 mRNA 翻译而来的。
Biosynthesis of glycosylphosphatidylinositol (GPI) is initiated by an unusually complex GPI-N-acetylglucosaminyltransferase (GPI-GnT) consisting of at least six proteins. Here, we report that human GPI-GnT requires another component, termed PIG-Y, a 71 amino acid protein with two transmembrane domains. The Burkitt lymphoma cell line Daudi, severely defective in the surface expression of GPI-anchored proteins, was a null mutant of PIG-Y. A complex of six components was formed without PIG-Y. PIG-Y appeared to be directly associated with PIG-A, implying that PIG-Y is the key molecule that regulates GPI-GnT activity by binding directly to the catalytic subunit PIG-A. PIG-Y is probably homologous to yeast Eri1p, a component of GPI-GnT. We did not obtain evidence for a functional linkage between GPI-GnT and ras GTPases in mammalian cells as has been reported for yeast cells. A single transcript encoded PIG-Y and, to its 5' side, another protein PreY that has homologues in a wide range of organisms and is characterized by a conserved domain termed DUF343. These two proteins are translated from one mRNA by leaky scanning of the PreY initiation site.