A membrane protein complex mediates retro-translocation from the ER lumen into the cytosol
A membrane protein complex mediates retro-translocation from the ER lumen into the cytosol
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DOI：
10.1038/nature02656
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发表时间：
2004-06-24
期刊：
影响因子：
64.8
通讯作者：
Rapoport, TA
中科院分区：
文献类型：
--
作者：
Ye, YH;Shibata, Y;Rapoport, TA
通过逆转录移位从内质网(ER)中清除错误折叠的蛋白质是对ER应激的一种重要的生理适应。这一过程需要识别内质网管腔中的底物，并随后通过胞质p97ATPase在膜上移动。在这里，我们在哺乳动物的内质网中发现了一个连接这两个事件的p97相互作用的膜蛋白复合体。该复合体的中心成分Derlin-1是Der1的同源物，Der1是一种酵母蛋白，其失活阻止了错误折叠的内质网蛋白的消除。当底物穿过细胞膜时，Derlin-1与不同的底物结合，而线虫中Derlin-1的失活会导致内质网应激。Derlin-1与病毒编码的ER蛋白US11以及VIMP相互作用，US11是一种病毒编码的ER蛋白，它专门针对内质网输出的MHC I类重链，VIMP是一种新的膜蛋白，它招募了p97 ATPase及其辅因子。
Elimination of misfolded proteins from the endoplasmic reticulum (ER) by retro-translocation is an important physiological adaptation to ER stress. This process requires recognition of a substrate in the ER lumen and its subsequent movement through the membrane by the cytosolic p97 ATPase. Here we identify a p97-interacting membrane protein complex in the mammalian ER that links these two events. The central component of the complex, Derlin-1, is a homologue of Der1, a yeast protein whose inactivation prevents the elimination of misfolded luminal ER proteins. Derlin-1 associates with different substrates as they move through the membrane, and inactivation of Derlin-1 in C. elegans causes ER stress. Derlin-1 interacts with US11, a virally encoded ER protein that specifically targets MHC class I heavy chains for export from the ER, as well as with VIMP, a novel membrane protein that recruits the p97 ATPase and its cofactor.