The engagement of Sec61p in the ER dislocation process.

The engagement of Sec61p in the ER dislocation process.
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Sec61p 参与 ER 错位过程。

DOI:
10.1016/s1097-2765(00)80222-1
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发表时间:
1999
期刊:
影响因子:
16
通讯作者:
Schekman,R
Schekman,R
中科院分区:
生物学1区
文献类型:
--
作者:
Zhou,M;Schekman,R

文献摘要

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Sec61p包括内质网(ER)通道,新生多肽通过该通道输入,并从该通道输出或错位折叠的蛋白质返回细胞质。我们设计了一种基因筛选,用于检测来自sec61的错位特异性突变等位基因。利用未折叠蛋白反应来报道错误折叠蛋白在内质网中的积累。分离的三个sec61等位基因完全精通蛋白质转运到内质网,但在消除错误折叠的内质网底物和短寿命的内质网跨膜模型蛋白方面存在缺陷,否则在野生型细胞中会被细胞质蛋白水解迅速降解。我们的研究结果表明,Sec61p的第四个腔袢和第三个跨膜结构域显著影响位错。我们认为sec61易位子的独特特征指导了双向易位过程。
Sec61p comprises the endoplasmic reticulum (ER) channel through which nascent polypeptides are imported and from which malfolded proteins have been suggested to be exported, or dislocated, back to the cytoplasm. We have devised a genetic screen for dislocation-specific mutant alleles ofSEC61fromS. cerevisiaeby employing the unfolded protein response to report on the accumulation of misfolded proteins in the ER. Three of the isolatedsec61alleles are fully proficient in protein translocation into the ER, but defective in the elimination of a misfolded ER luminal substrate and a short-lived ER membrane-spanning model protein, which are otherwise rapidly degraded by cytoplasmic proteolysis in wild-type cells. Our results point to the fourth luminal loop and third transmembrane domain of Sec61p that markedly influence dislocation. We suggest that distinct features of the Sec61-translocon direct the two-way translocation processes.