ERdj5 is required as a disulfide reductase for degradation of misfolded proteins in the ER
ERdj5 is required as a disulfide reductase for degradation of misfolded proteins in the ER
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DOI：
10.1126/science.1159293
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发表时间：
2008-07-25
期刊：
影响因子：
56.9
通讯作者：
Nagata, Kazuhiro
中科院分区：
文献类型：
--
作者：
Ushioda, Ryo;Hoseki, Jun;Nagata, Kazuhiro
膜蛋白和分泌蛋白协同进入内质网并在内质网中折叠。错误折叠或未组装的蛋白质通过称为ER相关降解（ERAD）的过程被丢弃，该过程涉及它们向胞质溶胶中的逆易位。ERAD底物通常含有二硫键，必须在它们的逆转位之前被切割。在此，我们发现ER驻留蛋白ERdj 5具有还原酶活性，切割错误折叠蛋白的二硫键，并通过其与EDEM（ER降解增强α-甘露糖苷酶样蛋白）和ER驻留伴侣BiP的物理和功能缔合来加速ERAD。因此，ERdj 5是超分子ERAD复合物的成员，其识别并展开错误折叠的蛋白质以使其有效地逆转位。
Membrane and secretory proteins cotranslationally enter and are folded in the endoplasmic reticulum ( ER). Misfolded or unassembled proteins are discarded by a process known as ER- associated degradation ( ERAD), which involves their retrotranslocation into the cytosol. ERAD substrates frequently contain disulfide bonds that must be cleaved before their retrotranslocation. Here, we found that an ER- resident protein ERdj5 had a reductase activity, cleaved the disulfide bonds of misfolded proteins, and accelerated ERAD through its physical and functional associations with EDEM ( ER degradation- enhancing alpha-mannosidase-like protein) and an ER- resident chaperone BiP. Thus, ERdj5 is a member of a supramolecular ERAD complex that recognizes and unfolds misfolded proteins for their efficient retrotranslocation.