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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 | 2023/09 |
| 形態種別 | 研究論文 |
| 査読 | 査読あり |
| 標題 | Mechanistic characterization of disulfide bond reduction of an ERAD substrate mediated by cooperation between ERdj5 and BiP. |
| 執筆形態 | その他 |
| 掲載誌名 | The Journal of biological chemistry |
| 掲載区分 | 国外 |
| 巻・号・頁 | 299(11),pp.105274 |
| 著者・共著者 | Xiaohan Cai,Shogo Ito,Kentaro Noi,Michio Inoue,Ryo Ushioda,Yukinari Kato,Kazuhiro Nagata,Kenji Inaba |
| 概要 | Endoplasmic reticulum (ER)-associated degradation (ERAD) is a protein quality control process that eliminates misfolded proteins from the ER. DnaJ homolog subfamily C member 10 (ERdj5) is a protein disulfide isomerase (PDI) family member that accelerates ER-associated degradation (ERAD) by reducing disulfide bonds of aberrant proteins with the help of an ER-resident chaperone BiP. However, the detailed mechanisms by which ERdj5 acts in concert with BiP are poorly understood. In this study, we reconstituted an in vitro system that monitors ERdj5-mediated reduction of disulfide-linked J-chain oligomers, known to be physiological ERAD substrates. Biochemical analyses using purified proteins revealed that J-chain oligomers were reduced to monomers by ERdj5 in a stepwise manner via trimeric and dimeric intermediates, and BiP synergistically enhanced this action in an ATP-dependent manner. Single-molecule observations of ERdj5-catalyzed J-chain disaggregation using high-speed atomic force microscopy (HS-AFM) demonstrated the stochastic release of small J-chain oligomers through repeated actions of ERdj5 on peripheral and flexible regions of large J-chain aggregates. Using systematic mutational analyses, ERAD substrate disaggregation mediated by ERdj5 and BiP was dissected at the molecular level. |
| DOI | 10.1016/j.jbc.2023.105274 |
| PMID | 37739037 |