DsbC

Related Reading

Introductions of Disulfide Bond

The disulfide bond, or S-S bond, is a covalent bond between sulfur atoms in the form of -S-S- formed by the oxidation of 2 sulfhydryl groups. The sulfhydryl groups of the 2 cysteine (Cys for short) residues on the peptide chain can undergo oxidation to form a disulfide bond; along with the formation of the disulfide bond, the cysteine residues are transformed into cystine residues. Disulfide bonds play a very important role in maintaining the molecular structure of proteins.

Role of Disulfide Bonds

Disulfide bonds are important for the proper folding of proteins and the formation and maintenance of higher structures. The formation of disulfide bond forces the amino acid residues in different regions of the same or different peptide chains to group together, thus the peptide chains fold rapidly and form a stable spatial topology, the number of amino acid residues in this region is highly dense; meanwhile the hydrophobic amino acid residues surround the disulfide bond, which can form a local hydrophobic center and refuse water molecules to enter the interior of the peptide to break the hydrogen bond. It facilitates the formation of a stable region of higher structure. Since disulfide bonds can bridge different regions of the peptide chain, they are sometimes referred to as disulfide bridges.

Background

DsbA is responsible for the oxidation of two sulfhydryl groups to form disulfide bonds, DsbB is responsible for the reoxidation of DsbA. DsbC and DsbG are responsible for the correction of abnormal disulfide bonds introduced by DsbA, DsbD is responsible for the re-reduction of DsbC and DsbG. Their molecular chaperone functions are independent of disulfide-forming enzyme activity and have a significant contribution to disulfide-forming enzyme activity. Based on the functional properties of Dsb proteins, there are many successful examples of using them to express exogenous proteins, especially disulfide-bond-containing proteins, in E. coli as hosts.

Discovery

In 1994 Missiakas et al. identified and functionally analyzed the presence of DsbC proteins in E. coli (the gene was initially called xprA). Previously, Shevchik et al. were the first to identify a gene named dsbC in Erwinia chrysanthemi whose product could compensate for the E. coli dsbA mutation, which causes a disorder in E. coli periplasmic lumen protein disulfide bond formation. E. coli dsbC deletion mutant strains accumulate many reduced forms of disulfide-containing proteins in their periplasmic lumen that can be rescued by adding oxidized dithiothreitol (DTT) or cysteine or by expressing multiple copies of dsbA. The E. coli DsbC precursor protein has a mass of 25.5 kD and is subsequently processed into a mature protein of 23.3 kD.

DsbC

Disulfide bond-forming protein B (DsbB) is a protein component of the pathway that leads to the formation of disulfide bonds in periplasmic proteins of E. coli and other bacteria. In Bacillus subtilis, it is known as BdbC.

Structure

DsbB protein oxidizes the periplasmic protein DsbA, which in turn oxidizes cysteines in other periplasmic proteins to form disulfide bonds. DsbB acts as a redox potential sensor across the cytoplasmic membrane. It is a membrane protein that spans the membrane four times, with both the N-terminal and C-terminal ends of the protein in the cytoplasm. Each periplasmic structural domain of the protein has two essential cysteines. The two cysteines in the first periplasmic domain are in the Cys-XY-Cys configuration, which is characteristic of the active sites of other proteins involved in disulfide bond formation, including DsbA and protein disulfide bond isomerases.