A membrane protein required for dislocation of misfolded proteins from the ER
A membrane protein required for dislocation of misfolded proteins from the ER
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DOI：
10.1038/nature02592
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发表时间：
2004-06-24
期刊：
影响因子：
64.8
通讯作者：
Ploegh, HL
中科院分区：
文献类型：
--
作者：
Lilley, BN;Ploegh, HL
在内质网（ER）中插入后，在那里无法折叠的蛋白质会被破坏。通过一种称为错位的过程，这些错误折叠的蛋白质到达细胞质中，在那里泛素化、去糖基化，最后蛋白酶体的蛋白水解作用处理掉不需要的多肽。从内质网提取错误折叠蛋白质所涉及的机制还不清楚。人巨细胞病毒编码的糖蛋白US2和US11催化I类主要组织相容性复合体（MHC）产物的错位，导致它们迅速降解。在此我们表明，US11利用其跨膜结构域将I类MHC产物招募到酵母Der1p的一种人同源物上，Der1p是降解一部分错误折叠的内质网蛋白质所必需的一种蛋白质。我们表明，这种蛋白质Derlin - 1对于US11（而非US2）催化的I类MHC分子的降解是必不可少的。我们得出结论，Derlin - 1是从哺乳动物内质网提取某些异常折叠蛋白质的一个重要因素。
After insertion into the endoplasmic reticulum ( ER), proteins that fail to fold there are destroyed. Through a process termed dislocation such misfolded proteins arrive in the cytosol, where ubiquitination, deglycosylation and finally proteasomal proteolysis dispense with the unwanted polypeptides. The machinery involved in the extraction of misfolded proteins from the ER is poorly defined. The human cytomegalovirus-encoded glycoproteins US2 and US11 catalyse the dislocation of class I major histocompatibility complex (MHC) products, resulting in their rapid degradation. Here we show that US11 uses its transmembrane domain to recruit class I MHC products to a human homologue of yeast Der1p, a protein essential for the degradation of a subset of misfolded ER proteins. We show that this protein, Derlin-1, is essential for the degradation of class I MHC molecules catalysed by US11, but not by US2. We conclude that Derlin-1 is an important factor for the extraction of certain aberrantly folded proteins from the mammalian ER.