3APS

Crystal structure of Trx4 domain of ERdj5

Summary for 3APS

• Entry DOI: 10.2210/pdb3aps/pdb
• Related: 3APO 3APQ
• Descriptor: DnaJ homolog subfamily C member 10, SULFATE ION, GLYCEROL, ... (4 entities in total)
• Functional Keywords: thioredoxin fold, cxxc motif, endoplasmic reticulum, oxidoreductase
• Biological source: Mus musculus (MOUSE)
• Cellular location: Secreted (Potential): Q9DC23
• Total number of polymer chains: 2
• Total formula weight: 28074.31

Authors

Inaba, K.,Suzuki, M.,Nagata, K. (deposition date: 2010-10-20, release date: 2011-04-20, Last modification date: 2024-10-23)

Primary citation

Hagiwara, M.,Maegawa, K.,Suzuki, M.,Ushioda, R.,Araki, K.,Matsumoto, Y.,Hoseki, J.,Nagata, K.,Inaba, K.
Structural basis of an ERAD pathway mediated by the ER-resident protein disulfide reductase ERdj5.
Mol.Cell, 41:432-444, 2011

PubMed Abstract: 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.

PubMed: 21329881
DOI: 10.1016/j.molcel.2011.01.021

Experimental method

X-RAY DIFFRACTION (1.9 Å)