Thiol-disulfide oxidoreductases catalyse the formation, disruption or isomerization of disulfide bonds in proteins. Disulfide bonds formed between pairs of cysteine residues are crucial for the stability in many proteins, while in others, such bonds can cause problems for example by preventing folding into the correct three-dimensional structure. To regulate formation of the required disulfide bonds, as well as breaking of dysfunctional ones, most cells contain intricate disulfide bond regulatory systems. Little is known about such systems in the cell envelope of Gram-positive bacteria.
Our research concerns proteins involved in thiol-disulfide inter-conversion on the outer (periplasmic) side of the cytoplasmic membrane in Bacillus subtilis. Eight membrane-bound thiol-disulfide oxidoreductases have so far been identified. The physiological functions for six of the proteins, BdbA, BdbB, BdbC, BdbD, CcdA and ResA, have been revealed; they are important for antibiotic biosynthesis, uptake of DNA, and cytochrome c maturation. One protein, StoA, is required for efficient synthesis of endospore cortex but the molecular basis for this is not yet understood. The function of one protein, YneN, remains completely enigmatic. Among our goals is now to find substrate proteins for the identified thiol-disulfide oxidoreductases and to understand how the specific interactions between thiol-disulfide oxidoreductases are governed.