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| DOI | 10.1126/science.aaz2449 |
| Structural basis of ER-associated protein degradation mediated by the Hrd1 ubiquitin ligase complex | |
| [无可用作者姓名] | |
| 发表日期 | 2020 |
| ISSN | 0036-8075 |
| 卷号 | 368期号:6489 |
| 英文摘要 | Misfolded luminal endoplasmic reticulum (ER) proteins undergo ER-associated degradation (ERAD-L): They are retrotranslocated into the cytosol, polyubiquitinated, and degraded by the proteasome. ERAD-L is mediated by the Hrd1 complex (composed of Hrd1, Hrd3, Der1, Usa1, and Yos9), but the mechanism of retrotranslocation remains mysterious. Here, we report a structure of the active Hrd1 complex, as determined by cryo–electron microscopy analysis of two subcomplexes. Hrd3 and Yos9 jointly create a luminal binding site that recognizes glycosylated substrates. Hrd1 and the rhomboid-like Der1 protein form two “half-channels” with cytosolic and luminal cavities, respectively, and lateral gates facing one another in a thinned membrane region. These structures, along with crosslinking and molecular dynamics simulation results, suggest how a polypeptide loop of an ERAD-L substrate moves through the ER membrane. © 2020 American Association for the Advancement of Science. All rights reserved. |
| 关键词 | Hrd1 ubiquitin ligase complexHrd3 proteinmembrane proteinpolypeptiderhomboid like Der1 proteinubiquitin protein ligaseunclassified drugYos9 proteinbiodegradationcell componentelectron microscopyenzymemolecular analysisproteinultrastructureArticlebinding sitecarboxy terminal sequencecontrolled studycryoelectron microscopycytosolendoplasmic reticulumenzyme substrateenzyme substrate complexfungal strainglycosylationmicellemolecular dynamicspriority journalprotein cross linkingprotein degradationprotein functionprotein misfoldingprotein structureyeast |
| 语种 | 英语 |
| 来源机构 | Science |
| 文献类型 | 期刊论文 |
| 条目标识符 | http://gcip.llas.ac.cn/handle/2XKMVOVA/133537 |
| 推荐引用方式 GB/T 7714 | [无可用作者姓名]. Structural basis of ER-associated protein degradation mediated by the Hrd1 ubiquitin ligase complex[J]. Science,2020,368(6489). |
| APA | [无可用作者姓名].(2020).Structural basis of ER-associated protein degradation mediated by the Hrd1 ubiquitin ligase complex.,368(6489). |
| MLA | [无可用作者姓名]."Structural basis of ER-associated protein degradation mediated by the Hrd1 ubiquitin ligase complex".368.6489(2020). |
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