The Crystal Structure of Yeast Protein Disulfide Isomerase Suggests Cooperativity Between Its Active Sites

Journal Article · Sun Jan 01 04:00:00 EST 2006 · Cell

DOI:https://doi.org/10.1016/j.cell.2005.10.044· OSTI ID:914293

Tian, G; Xiang, S; Noiva, R; Lennarz, W; Schindelin, H

Protein disulfide isomerase plays a key role in catalyzing the folding of secretory proteins. It features two catalytically inactive thioredoxin domains inserted between two catalytically active thioredoxin domains and an acidic C-terminal tail. The crystal structure of yeast PDI reveals that the four thioredoxin domains are arranged in the shape of a twisted 'U' with the active sites facing each other across the long sides of the 'U.' The inside surface of the 'U' is enriched in hydrophobic residues, thereby facilitating interactions with misfolded proteins. The domain arrangement, active site location, and surface features strikingly resemble the Escherichia coli DsbC and DsbG protein disulfide isomerases. Biochemical studies demonstrate that all domains of PDI, including the C-terminal tail, are required for full catalytic activity. The structure defines a framework for rationalizing the differences between the two active sites and their respective roles in catalyzing the formation and rearrangement of disulfide bonds.

• Research Organization: Brookhaven National Laboratory (BNL) National Synchrotron Light Source
• Sponsoring Organization: Doe - Office Of Science
• DOE Contract Number: AC02-98CH10886
• OSTI ID: 914293
• Report Number(s): BNL--78861-2007-JA
• Journal Information: Cell, Journal Name: Cell Journal Issue: 1 Vol. 124; ISSN 0092-8674; ISSN CELLB5
• Country of Publication: United States
• Language: English

Related Subjects

36 MATERIALS SCIENCE
CRYSTAL STRUCTURE
DISULFIDES
ESCHERICHIA COLI
ISOMERASES
PROTEINS
RESIDUES
SHAPE
YEASTS
national synchrotron light source