dsbAdsbB

DsbADsbB refers to the bacterial disulfide-bond formation system formed by DsbA and DsbB. In many Gram-negative bacteria, this pair operates in the periplasm to catalyze the formation of disulfide bonds in exported or secreted proteins, helping them fold correctly. DsbA is a small, soluble periplasmic protein with a thioredoxin-like fold and an active-site motif, typically Cys-Gly-Tyr-Cys, that directly introduces disulfide bonds into substrate proteins. DsbB is an inner membrane protein that reoxidizes reduced DsbA after it has donated its disulfide to a substrate.

Mechanism: DsbA transfers its disulfide to a substrate, oxidizing the substrate and becoming reduced. DsbB reoxidizes DsbA by accepting electrons from DsbA’s active-site cysteines and passing them to the quinone pool of the inner-membrane electron transport chain, thereby regenerating oxidized DsbA for another catalytic cycle. This oxidative folding cycle is part of a broader network that maintains periplasmic redox balance, including enzymes such as DsbC and DsbD that can isomerize or shuttle reducing equivalents as needed.

Structure and genetics: DsbA is a soluble periplasmic protein; DsbB spans the inner membrane with multiple transmembrane segments and contains cysteine residues essential for its redox activity. In many bacteria, dsbA and dsbB are located near each other in the genome and may be co-regulated, with some species encoding multiple DsbA paralogs or DsbB homologs.

Biological and clinical relevance: The DsbA-DsbB system is required for proper oxidative folding of a wide range of extracytoplasmic proteins, including many virulence factors such as adhesins and toxins. Because disruption of this system can attenuate virulence without necessarily inhibiting growth, it is a focus of interest for antivirulence strategies and antimicrobial development.