Abstract
Disulfide bonds represent versatile posttranslational modifications whose roles encompass the structure, catalysis, and regulation of protein function. Due to the oxidizing nature of the extracellular environment, disulfide bonds found in secreted proteins were once believed to be inert. This notion has been challenged by the discovery of redox-sensitive disulfides that, once cleaved, can lead to changes in protein activity. These functional disulfides are twisted into unique configurations, leading to high strain and potential energy. In some cases, cleavage of these disulfides can lead to a gain of function in protein activity. Thus, these motifs can be referred to as switches. We describe the couples that control redox in the extracellular environment, examine several examples of proteins with switchable disulfides, and discuss the potential applications of disulfides in molecular biology.