Dsbproteinsystem

The Dsb protein system, short for disulfide bond system, is a network of thiol-disulfide oxidoreductases that control the formation, isomerization, and, in some cases, reduction of disulfide bonds in extracytoplasmic proteins. It is primarily studied in Gram-negative bacteria, where most of the components reside in the periplasm, but related systems also operate in other bacterial lineages. The core purpose of the Dsb system is to ensure that secreted and periplasmic proteins fold correctly by establishing the proper disulfide bond pattern, which is essential for stability and function.

In Escherichia coli and many related bacteria, the pathway centers on DsbA, DsbB, DsbC, DsbG, and DsbD. DsbA is a soluble periplasmic thiol oxidase that directly introduces disulfide bonds into substrate proteins as they fold. DsbA is reoxidized by the inner-membrane protein DsbB, which transfers electrons to the quinone pool and thereby regenerates DsbA in its active, oxidized form. DsbC and DsbG are periplasmic disulfide isomerases that correct mispaired or improperly formed disulfides; they are maintained in a reduced state by DsbD, a membrane-anchored conduit that transfers reducing equivalents from the cytoplasm to the periplasm via thioredoxin-like domains.

Additional periplasmic reductases such as DsbE and DsbF can participate in reducing specific substrates. The Dsb system is essential for the maturation of many secreted and outer-murface proteins, including some virulence factors in pathogenic species, and its organization varies across bacterial taxa.