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Publication Abstract from PubMed

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.

Structural basis of an ERAD pathway mediated by the ER-resident protein disulfide reductase ERdj5.,Hagiwara M, Maegawa K, Suzuki M, Ushioda R, Araki K, Matsumoto Y, Hoseki J, Nagata K, Inaba K Mol Cell. 2011 Feb 18;41(4):432-44. PMID:21329881^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.