Structurally related Spc1p and Spc2p of yeast signal peptidase complex are functionally distinct
Structurally related Spc1p and Spc2p of yeast signal peptidase complex are functionally distinct
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DOI：
10.1074/jbc.271.46.29094
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发表时间：
1996-11-15
影响因子：
4.8
通讯作者：
Fang, H
中科院分区：
文献类型：
--
作者：
Mullins, C;Meyer, HA;Fang, H
哺乳动物信号肽酶复合物的两个亚基 SPC12 和 SPC25 具有相似的膜拓扑结构，每种蛋白质的大部分都面向细胞质。这种相似性可能表明这些蛋白质在信号肽酶活性中发挥冗余功能。在本研究中，我们通过分析 SPC12 和 SPC25、Spc1p 和 Spc2p 的酵母同源物解决了这个问题。我们表明，Spc1p 和 Spc2p 对于信号肽酶活性和酵母细胞的生长都不是必需的，并且编码 Spc1p 和 Spc2p 的基因中的无效突变具有综合致死性，而条件突变影响 Sec11p（酵母信号肽酶的重要亚基）。然而，编码Spc1p的高拷贝质粒抑制条件性sec11突变，而编码Spc2p的相应质粒不抑制sec11。此外，Spc2p（而非 Spc1p）对于高温下的信号肽酶活性和细胞活力很重要。这些结果表明，虽然 Spc1p 和 Spc2p 都是非催化性的，但它们在功能上是不同的。还提供了证据表明，缺乏 Spc1p 和 Spc2p 的双突变体相对于野生型酵母细胞生长良好，表明缺少至少两个亚基的信号肽酶复合物足以维持体内信号肽酶活性。
Two subunits of the mammalian signal peptidase complex, SPC12 and SPC25, share similar membrane topologies with the majority of each protein oriented toward the cytoplasm. Such similarities may suggest that these proteins perform redundant functions in signal peptidase activity. In the present study, we addressed this issue through analysis of the yeast homologs to SPC12 and SPC25, Spc1p and Spc2p. We show that both Spc1p and Spc2p are nonessential for signal peptidase activity and growth of yeast cells and that null mutations in the genes encoding Spc1p and Spc2p are synthetically lethal with a conditional mutation affecting Sec11p, an essential subunit of yeast signal peptidase. However, a high copy plasmid encoding Spc1p suppresses the conditional sec11 mutation, whereas the corresponding plasmid encoding Spc2p does not suppress sec11. Moreover, Spc2p, but not Spc1p, is important for signal peptidase activity and cell viability at high temperatures. These results indicate that although both Spc1p and Spc2p are noncatalytic, they are functionally distinct. Evidence is also presented that a double mutant lacking Spc1p and Spc2p grows well relative to wild type yeast cells, indicating that the signal peptidase complex missing at least two of its subunits is sufficient for signal peptidase activity in vivo.