Sec61p is required for ERAD-L: genetic dissection of the translocation and ERAD-L functions of Sec61P using novel derivatives of CPY.
Sec61p is required for ERAD-L: genetic dissection of the translocation and ERAD-L functions of Sec61P using novel derivatives of CPY.
复制标题
DOI：
10.1074/jbc.m803054200
复制
发表时间：
2008-12-05
影响因子：
4.8
通讯作者：
Stirling, Colin J.
中科院分区：
文献类型：
--
作者：
Willer, Martin;Forte, Gabriella M. A.;Stirling, Colin J.
内质网 (ER) 中错误折叠的蛋白质被输出到细胞质中，被蛋白酶体降解，这一过程称为 ER 相关降解 (ERAD)。 CPY* 是一种特征明确的 ERAD 底物，其降解取决于 Hrd1 复合物。然而，尽管该复合物的一些成分的功能是已知的，但蛋白质位错通道的性质仍然不清楚。 Sec61p 被认为是一个明显的候选者，因为它作为蛋白质传导通道，多肽最初通过该通道转运到内质网中。然而，目前还不可能从功能上剖析 Sec61p 在错位中的任何作用及其在易位中的基本功能。通过改变一系列新型 ERAD 底物的易位特性，我们能够将这两个事件分开，并发现功能性 Sec61p 对于 ERAD-L 途径至关重要。
Misfolded proteins in the endoplasmic reticulum (ER) are exported to the cytosol for degradation by the proteasome in a process known as ER-associated degradation (ERAD). CPY* is a well characterized ERAD substrate whose degradation is dependent upon the Hrd1 complex. However, although the functions of some of the components of this complex are known, the nature of the protein dislocation channel remains obscure. Sec61p has been suggested as an obvious candidate because of its role as a protein-conducting channel through which polypeptides are initially translocated into the ER. However, it has not yet been possible to functionally dissect any role for Sec61p in dislocation from its essential function in translocation. By changing the translocation properties of a series of novel ERAD substrates, we are able to separate these two events and find that functional Sec61p is essential for the ERAD-L pathway.