The ubiquitin-domain protein HERP forms a complex with components of the endoplasmic reticulum associated degradation pathway
The ubiquitin-domain protein HERP forms a complex with components of the endoplasmic reticulum associated degradation pathway
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DOI：
10.1016/j.jmb.2005.10.020
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发表时间：
2005-12-16
影响因子：
5.6
通讯作者：
Seeger, M
中科院分区：
文献类型：
--
作者：
Schulze, A;Standera, S;Seeger, M
为了消除积聚在内质网（ER）中的错误折叠蛋白，细胞主要依赖于泛素-蛋白酶体依赖性ER相关蛋白降解（ERAD）。ERAD底物被蛋白酶体蛋白水解，需要它们的泛素化和从ER到cytoplasm.Here，我们描述了一个高分子量的蛋白质复合物与ER膜，这有利于ERAD。它含有泛素结构域蛋白（UDP）HERP、泛素蛋白连接酶HRD 1以及逆转录易位因子p97、Derlin-1和VIMP。这些ERAD蛋白的结构表明，p97直接与ERAD复合物中的Derlin-1和HRD 1相互作用，而HERP则直接与HRD 1相互作用。我们认为，ERAD蛋白的泛素化以及蛋白质的逆向转运都是通过这种模块化的蛋白复合物完成的，这使得ERAD中这些连续的步骤能够紧密协调。(c)2005爱思唯尔有限公司保留所有权利。
To eliminate misfolded proteins that accumulate in the endoplasmic reticulum (ER) the cell mainly relies on ubiquitin-proteasome dependent ER-associated protein degradation (ERAD). Proteolysis of ERAD substrates by the proteasome requires their ubiquitylation and retrotranslocation from the ER to the cytoplasm.Here we describe a high molecular mass protein complex associated with the ER membrane, which facilitates ERAD. It contains the ubiquitin domain protein (UDP) HERP, the ubiquitin protein ligase HRD1, as well as the retro-translocation factors p97, Derlin-1 and VIMP. Our data on the structural arrangement of these ERAD proteins suggest that p97 interacts directly with membrane-resident components of the complex including Derlin-1 and HRD1, while HERP binds directly to HRD1.We propose that ubiquitylation, as well as retro-translocation of proteins from the ER are performed by this modular protein complex, which permits the close coordination of these consecutive steps within ERAD. (c) 2005 Elsevier Ltd. All rights reserved.