PDBsum entry 1jzd

Oxidoreductase

PDB id: 1jzd

Contents

Protein chains

219 a.a. *

118 a.a. *

Waters ×124

* Residue conservation analysis

References listed in PDB file

Key reference

Title

The disulfide bond isomerase dsbc is activated by an immunoglobulin-Fold thiol oxidoreductase: crystal structure of the dsbc-Dsbdalpha complex.

Authors

P.W.Haebel, D.Goldstone, F.Katzen, J.Beckwith, P.Metcalf.

Ref.

EMBO J, 2002, 21, 4774-4784. [DOI no: 10.1093/emboj/cdf489]

PubMed id

12234918

Abstract

The Escherichia coli disulfide bond isomerase DsbC rearranges incorrect disulfide bonds during oxidative protein folding. It is specifically activated by the periplasmic N-terminal domain (DsbDalpha) of the transmembrane electron transporter DsbD. An intermediate of the electron transport reaction was trapped, yielding a covalent DsbC-DsbDalpha complex. The 2.3 A crystal structure of the complex shows for the first time the specific interactions between two thiol oxidoreductases. DsbDalpha is a novel thiol oxidoreductase with the active site cysteines embedded in an immunoglobulin fold. It binds into the central cleft of the V-shaped DsbC dimer, which assumes a closed conformation on complex formation. Comparison of the complex with oxidized DsbDalpha reveals major conformational changes in a cap structure that regulates the accessibility of the DsbDalpha active site. Our results explain how DsbC is selectively activated by DsbD using electrons derived from the cytoplasm.

Figure 3.
Figure 3 Conformational changes during the thiol−disulfide exchange reaction between DsbC and DsbD . (A) Ribbon presentation of the DsbC dimer showing the open (white) and closed (blue and green) conformation of the molecule. In the open conformation, the sulfur atoms (yellow spheres) of the two DsbC active site Cys98 are 38 Å apart. DsbC assumes a closed conformation on binding to DsbD and the hinge movements observed in the DsbC linker helices result in the reduction of the distance between the active sites to 29 Å in the closed form. (B) Representation of the open (red) and shielded (white) form of the DsbD active site. In the open form observed in the DsbC−DsbD complex, the opening of the active site cap facilitates access to the DsbC binding pocket. In the shielded oxidized form of DsbD , the binding pocket is protected from the environment by Phe70, which makes close van der Waals interactions with the active site disulfide (yellow). Phe70 moves 13 Å from its position in oxidized DsbD .

Figure 4.
Figure 4 Interactions of the two DsbC active sites with DsbD residues. (A) Stereo diagram of the primary binding site showing the DsbC active site interacting with DsbD . The primary binding surface of DsbD is shown colored according to the calculated electrostatic potential using GRASP. Negative charges are colored red and positive charges are in blue. Important DsbC residues (Ile96−Leu104, Gly181−Val185) are shown in blue ball-and-stick and cartoon representation. DsbC residues are labeled in black and DsbD residues in green. DsbC Tyr100 binds into an uncharged pocket adjacent to the DsbD active site Cys109, which forms a disulfide bond with DsbC Cys98 and hydrogen bonds to the cis-proline loop, Thr182−Pro183. (B) Stereo diagram of the secondary binding site. The electrostatic surface of the DsbD secondary binding site is presented with DsbD residues labeled in green. The DsbC active region is shown in green ball-and-stick and ribbons representation with yellow labels. DsbD Asp21 interacts with the DsbC active site Cys98 and Gly99, while Tyr100 packs against DsbD Phe22.

The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (2002, 21, 4774-4784) copyright 2002.