Structural Basis of an ERAD Pathway Mediated by the ER-Resident Protein Disulfide Reductase ERdj5

Masatoshi Hagiwara, Ken ichi Maegawa, Mamoru Suzuki, Ryo Ushioda, Kazutaka Araki, Yushi Matsumoto, Jun Hoseki, Kazuhiro Nagata, Kenji Inaba

Research output: Contribution to journalArticlepeer-review

119 Citations (Scopus)


ER-associated degradation (ERAD) is an ER quality-control 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.

Original languageEnglish
Pages (from-to)432-444
Number of pages13
JournalMolecular Cell
Issue number4
Publication statusPublished - 2011 Feb 18


Dive into the research topics of 'Structural Basis of an ERAD Pathway Mediated by the ER-Resident Protein Disulfide Reductase ERdj5'. Together they form a unique fingerprint.

Cite this