Excluding the Cysteines♦
Disulfide Bond Formation and Cysteine Exclusion in Gram-positive Bacteria
♦ See referenced article, J. Biol. Chem. 2010, 285, 3300–3309
Computational modeling of cysteine incorporation patterns shows that exported proteins from Actinobacteria display an even number suggestive of disulfide bond formation (left), whereas proteins from Firmicutes preferentially exclude cysteines (right).
Secreted proteins in both bacteria and eukaryotes face the challenge of having to mature in a reactive, oxidizing environment. In Gram-negative bacteria, the secreted proteins mature in the periplasm with the aid of molecular chaperones and disulfide bond-forming machinery. However, in Gram-positive bacteria, which lack an outer membrane, proteins have to mature in the unregulated cell wall. How Gram-positive bacteria handle this is poorly understood, but in this Paper of the Week Robert Daniels and colleagues combined experimental and computational approaches to investigate the strategies Gram-positive bacteria employ to cope with a challenging environment. Their predictions indicated that aerobic Actinobacteria likely form disulfide bonds in their exported proteins, whereas aerobic Firmicutes generally exclude cysteines from their secreted proteins. In support of these predictions, Daniels and colleagues demonstrated that Firmicutes, but not Actinobacteria, can tolerate high levels of reductant and thus do not require disulfide-bonded proteins for growth; they also identified two different Dsb-like proteins in the Actinobacteria Corynebacterium glutamicum capable of catalyzing disulfide bond formation. These results demonstrate that Gram-positive bacteria have evolved at least two mechanisms to handle oxidative challenges in the cell wall: regulated disulfide bond formation and complete cysteine exclusion.
- © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.
