[1FT-3] 機能解析・細胞・イメージング (1P-49～1P-61)

[1P-55*] Mechanisms of ER-associated degradation pathway mediated by the cooperation of ERdj5 and BiP

^○Xiaohan Cai¹, 伊藤 翔悟¹, 野井 健太郎³, 井上 道雄², 潮田 亮⁴, 永田 和宏⁴, 稲葉 謙次^1,2 (1.東北大学生命科学研究科, 2.東北大学多元物質科学研究所, 3.大阪大学ナノサイエンスデザイン教育研究センター, 4.京都産業大学生命科学部)

ER-associate degradation (ERAD) is an ER quality control process that eliminates terminally misfolded proteins. ERdj5, a member of the PDI family, has been reported to play a key role in the clearance of aberrant proteins with the help of an ER-resident chaperone BiP. However, until now, the detailed molecular mechanism by which ERdj5 fulfills its function in concert with BiP in the ERAD pathway is still poorly understood. Here, we use disulfide-linked J-chain oligomers as a substrate, and succeeded in monitoring the sequential reduction of J-chain oligomers catalyzed by the cooperation of ERdj5 and BiP. ERdj5 consists of the N-terminal and C-terminal clusters with six tandem thioredoxin (Trx)-like domains and an inter-cluster flexible linker loop. Our biochemical studies showed that the C-terminal Trx4 domain catalyzes disulfide reduction of J-chain oligomers most efficiently, and that the restricted cluster dynamics led to the prevention of this reaction. Our results indicate a distinct role of each Trx-like domain of ERdj5 and the essentiality of ERdj5 conformational dynamics in promotion of ERAD.