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ウシオダ リョウ
USHIODA RYO
潮田 亮 所属 京都産業大学 生命科学部 先端生命科学科 職種 准教授 |
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| 言語種別 | 英語 |
| 発行・発表の年月 | 2011/02 |
| 形態種別 | 研究論文 |
| 標題 | Structural Basis of an ERAD Pathway Mediated by the ER-Resident Protein Disulfide Reductase ERdj5 |
| 執筆形態 | その他 |
| 掲載誌名 | Molecular Cell |
| 出版社・発行元 | Elsevier BV |
| 巻・号・頁 | 41(4),pp.432-444 |
| 著者・共著者 | Masatoshi Hagiwara,Ken-ichi Maegawa,Mamoru Suzuki,Ryo Ushioda,Kazutaka Araki,Yushi Matsumoto,Jun Hoseki,Kazuhiro Nagata,Kenji Inaba |
| 概要 | ER-associated degradation (ERAD) is an ER qualitycontrol process that eliminates terminally misfolded proteins. ERdj5 was recently discovered to be a key ER-resident PDI family member protein that accelerates ERAD by reducing incorrect disulfide bonds in misfolded glycoproteins recognized by EDEM1. We here solved the crystal structure of full-length ERdj5, thereby revealing that ERdj5 contains the N-terminal J domain and six tandem thioredoxin domains that can be divided into the N- and C-terminal clusters. Our systematic biochemical analyses indicated that two thioredoxin domains that constitute the C-terminal cluster form the highly reducing platform that interacts with EDEM1 and reduces EDEM1-recruited substrates, leading to their facilitated degradation. The pulse-chase experiment further provided direct evidence for the sequential movement of an ERAD substrate from calnexin to the downstream EDEM1-ERdj5 complex, and then to the retrotranslocation channel, probably through BiP. We present a detailed molecular view of how ERdj5 mediates ERAD in concert with EDEM1. |
| DOI | 10.1016/j.molcel.2011.01.021 |
| ISSN | 1097-2765 |
| NAID | 120003836694 |
| PermalinkURL | http://hdl.handle.net/2324/19148 |