Functional differences in yeast protein disulfide isomerases.

Functional differences in yeast protein disulfide isomerases.
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DOI:
10.1083/jcb.152.3.553
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发表时间:
2001-02-05
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Winther JR
Winther JR
中科院分区:
其他
文献类型:
--
作者:
Nørgaard P;Westphal V;Tachibana C;Alsøe L;Holst B;Winther JR

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PDI1是酵母中编码蛋白质二硫键异构酶的必需基因。然而,酿酒酵母基因组中还有另外四个与PDI1同源的非必需基因:MPD1、MPD2、EUG1和EPS1。我们已经研究了这些基因同时缺失的影响。在一些情况下,我们发现PDI1同源物在过表达时恢复pdi1缺失菌株的活力的能力依赖于一个或多个其他同源物的低内源水平的存在。这表明同系物在功能上是不可互换的。事实上,Mpd1p是唯一能够执行Pdi1p所有基本功能的同源物。此外,在硫氧还蛋白样结构域中存在具有CXXC基序的内源同系物,才能抑制EUG1(包含两个CXXS活性位点基序)的pdi1缺失。这凸显了蛋白质二硫键异构酶催化氧化的重要性。大多数突变组合在羧基肽酶Y折叠和糖链修饰方面都存在缺陷。然而,在不同的蛋白质二硫键异构酶缺失菌株中,对ER相关蛋白的降解没有显著影响。
PDI1 is the essential gene encoding protein disulfide isomerase in yeast. The Saccharomyces cerevisiae genome, however, contains four other nonessential genes with homology to PDI1: MPD1, MPD2, EUG1, and EPS1. We have investigated the effects of simultaneous deletions of these genes. In several cases, we found that the ability of the PDI1 homologues to restore viability to a pdi1-deleted strain when overexpressed was dependent on the presence of low endogenous levels of one or more of the other homologues. This shows that the homologues are not functionally interchangeable. In fact, Mpd1p was the only homologue capable of carrying out all the essential functions of Pdi1p. Furthermore, the presence of endogenous homologues with a CXXC motif in the thioredoxin-like domain is required for suppression of a pdi1 deletion by EUG1 (which contains two CXXS active site motifs). This underlines the essentiality of protein disulfide isomerase-catalyzed oxidation. Most mutant combinations show defects in carboxypeptidase Y folding as well as in glycan modification. There are, however, no significant effects on ER-associated protein degradation in the various protein disulfide isomerase-deleted strains.
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