DsbADsbC

DsbA and DsbC are periplasmic enzymes found in many Gram-negative bacteria that participate in the formation and maintenance of disulfide bonds in extracytoplasmic proteins. Together, they form part of the cellular disulfide bond (Dsb) system that ensures correct protein folding in the oxidative environment of the periplasm.

DsbA acts as a thiol-disulfide oxidoreductase that introduces disulfide bonds into unfolded substrate proteins. It cycles between an oxidized and reduced state and transfers its disulfide to client proteins, becoming reduced in the process. DsbA is typically reoxidized by another membrane protein, DsbB, which channels electrons into the respiratory chain, restoring DsbA’s oxidizing power for further rounds of catalysis. Substrates of DsbA include secreted enzymes, periplasmic proteins, and outer membrane components that require disulfide bonds for stability.

DsbC functions as a disulfide isomerase, correcting incorrectly formed disulfide bonds in substrates that have already acquired them but are mispaired. In most bacteria, DsbC operates as a homodimer and is kept in a reduced state by the oxidoreductase DsbD, which transfers reducing equivalents from the cytoplasm to the periplasm. This reduced DsbC can rearrange disulfide bonds until the correct configuration is achieved, acting as a proofreading factor in protein folding.

The DsbA–DsbC system may occur as separate proteins or, in some organisms, as fused or operon-linked components that coordinate their activities. Proper function of this pathway is important for the maturation of many periplasmic and secreted proteins, and in some pathogens it contributes to virulence by enabling correct folding of surface and secreted factors.