DsbA

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Introductions

DsbA is a bacterial thiol disulfide oxidoreductase (TDOR). DsbA is a key component of the Dsb (disulfide bond) family of enzymes. DsbA catalyzes intrachain disulfide bond formation as peptides emerge into the cell's periplasm.

Structure

Structurally, DsbA contains a thioredoxin domain with an inserted helical domain of unknown function. Like other thioredoxin-based enzymes, DsbA's catalytic site is a CXXC motif (CPHC in E. coli DsbA). The pair of cysteines may be oxidized (forming an internal disulfide) or reduced (as free thiols), and thus allows for oxidoreductase activity by serving as an electron pair donor or acceptor, depending on oxidation state. This reaction generally proceeds through a mixed-disulfide intermediate, in which a cysteine from the enzyme forms a bond to a cysteine on the substrate. DsbA is responsible for introducing disulfide bonds into nascent proteins. In equivalent terms, it catalyzes the oxidation of a pair of cysteine residues on the substrate protein. Most of the substrates for DsbA are eventually secreted, and include important toxins, virulence factors, adhesion machinery, and motility structures.

Effect of disulfide-bonded redox proteins (Dsb) on pathogenicity of pathogenic bacteria

Post-translational modification is an essential and important part of the protein maturation process, which can ensure the correct folding, and activity of the protein. And cysteine plays an important role in bacterial post-translational modifications. A disulfide bond oxidoredutase (Dsb) was found to be present in the bacterial inner membrane and periplasmic space, which enables transmembrane proteins with sulfhydryl groups to form intramolecular disulfide bonds, allowing them to fold properly and function accordingly. In addition, the secretory proteins secreted by bacteria to the outside of the cell, if the folding is completed in the cell, it is difficult to secrete the protein to the outside of the cell due to the spatial blockage when it passes through the cell membrane.

Effect of disulfide bond redox protein (Dsb) on pathogenicity of Escherichia coli

The formation of disulfide bonds in E. coli is in the periplasm and is catalyzed by the thiol-disulfide oxidoreductase DsbA. DsbA, the first identified disulfide bond redox protein, is a donor of disulfide compounds to newly synthesized periplasmic proteins and is reoxidized by DsbB, a second protein located in the inner membrane. DsbA and DsbB can form a complete chain of redox cycles that continuously drive the proper folding and functioning of substrate proteins in the cytosolic and periplasmic spaces. DsbA and DsbB proteins belong to the thioredoxin family. Both thioredoxins contain typical C-XX-C dithiol active site sequences and are conserved in Gram-negative bacteria. dsbC is another member of the disulfide isomerase family. The current study found that E. coli DsbA is closely related to the motility of its own flagellum, and when dsbA or dsbB is missing it leads to the deletion of E. coli. When dsbA or dsbB is absent, the P-loop protein (FlgI) of E. coli cannot synthesize disulfide bonds and thus cannot assemble the flagellum, and therefore loses motility.

Effect of disulfide-bonded redox protein (Dsb) on the pathogenicity of Vibrio cholerae

VcDsbA is a disulfide-bonded oxidoreductase in the periplasmic space of Vibrio cholerae, which is essential for Vibrio cholerae pathogenicity. VcDsbA is not only essential for the secretion of cholera toxin factors, but also, in the presence of bile salts, VcDsbA can activate the virulence of Vibrio cholerae by inducing TcpP to form a dimer, thereby activating the expression of the downstream virulence factor gene toxT. Therefore, Vc DsbA is also essential for the expression of ToxT, the main virulence regulator of Vibrio cholerae. In addition, VcDsbA can promote biofilm formation by enhancing the expression of MSHA in an in vitro environment.