3UEM

Crystal structure of human PDI bb'a' domains

Summary for 3UEM

• Entry DOI: 10.2210/pdb3uem/pdb
• Descriptor: Protein disulfide-isomerase, (4S,5S)-1,2-DITHIANE-4,5-DIOL (3 entities in total)
• Functional Keywords: protein disulfide isomerase, thioredoxin-like domain, chaperone
• Biological source: Homo sapiens (human)
• Cellular location: Endoplasmic reticulum lumen: P07237
• Total number of polymer chains: 1
• Total formula weight: 40900.02

Authors

Yu, J.,Wang, C.,Huo, L.,Feng, W.,Wang, C.-C. (deposition date: 2011-10-30, release date: 2011-11-23, Last modification date: 2024-03-20)

Primary citation

Wang, C.,Yu, J.,Huo, L.,Wang, L.,Feng, W.,Wang, C.-C.
Human protein-disulfide isomerase is a redox-regulated chaperone activated by oxidation of domain a'
J.Biol.Chem., 287:1139-1149, 2012

PubMed Abstract: Protein-disulfide isomerase (PDI), with domains arranged as abb'xa'c, is a key enzyme and chaperone localized in the endoplasmic reticulum (ER) catalyzing oxidative folding and preventing misfolding/aggregation of proteins. It has been controversial whether the chaperone activity of PDI is redox-regulated, and the molecular basis is unclear. Here, we show that both the chaperone activity and the overall conformation of human PDI are redox-regulated. We further demonstrate that the conformational changes are triggered by the active site of domain a', and the minimum redox-regulated cassette is located in b'xa'. The structure of the reduced bb'xa' reveals for the first time that domain a' packs tightly with both domain b' and linker x to form one compact structural module. Oxidation of domain a' releases the compact conformation and exposes the shielded hydrophobic areas to facilitate its high chaperone activity. Thus, the study unequivocally provides mechanistic insights into the redox-regulated chaperone activity of human PDI.

PubMed: 22090031
DOI: 10.1074/jbc.M111.303149

Experimental method

X-RAY DIFFRACTION (2.29 Å)