4EL1: Crystal Structure Of Oxidized Hpdi (abb'xa')

Citation:
Abstract
Abstract Aim: Human protein disulfide isomerase (hPDI) is a key enzyme and a redox-regulated chaperone responsible for oxidative protein folding in the endoplasmic reticulum. This work aims to reveal the molecular mechanism underlying the redox-regulated functions of hPDI by determining the crystal structures of hPDI in different redox states. Results: The structures of hPDI (abb'xa') in both the reduced and oxidized states showed that the four thioredoxin domains of a, b, b', and a' are arranged as a horseshoe shape with two CGHC active sites, respectively, in domains a and a' facing each other at the two ends. In reduced hPDI, domains a, b, and b' line up in the same plane, whereas domain a' twists approximately 45 degrees out. The two active sites are 27.6 A apart. In oxidized hPDI, the four domains are differently organized to stay in the same plane, and the distance between the active sites increases to 40.3 A. In contrast to the closed conformation of reduced hPDI, oxidized hPDI exists in an open state with more exposed hydrophobic areas and a larger cleft with potential for substrate binding. Innovation: This is the first report of the high-resolution structures of hPDI containing all four domains in both the reduced and the oxidized states. It reveals the redox-regulated structural dynamic properties of the protein. Conclusion: The redox-regulated open/closed conformational switch of hPDI endows the protein with versatile target-binding capacities for its enzymatic and chaperone functions. Antioxid. Redox Signal. 19, 44-53.
PDB ID: 4EL1Download
MMDB ID: 108998
PDB Deposition Date: 2012/4/10
Updated in MMDB: 2013/07
Experimental Method:
x-ray diffraction
Resolution: 2.88  Å
Source Organism:
Similar Structures:
Biological Unit for 4EL1: monomeric; determined by author and by software (PISA)
Molecular Components in 4EL1
Label Count Molecule
Protein (1 molecule)
1
Protein Disulfide-isomerase(Gene symbol: P4HB)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

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