| First Author | Hagiwara M | Year | 2011 |
| Journal | Mol Cell | Volume | 41 |
| Issue | 4 | Pages | 432-44 |
| PubMed ID | 21329881 | Mgi Jnum | J:170851 |
| Mgi Id | MGI:4947480 | Doi | 10.1016/j.molcel.2011.01.021 |
| Citation | Hagiwara M, et al. (2011) Structural basis of an ERAD pathway mediated by the ER-resident protein disulfide reductase ERdj5. Mol Cell 41(4):432-44 |
| abstractText | 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. |
