The roles of conditional disorder in redox proteins

Cells are constantly exposed to various oxidants, either generated endogenously due to metabolic activity or exogenously. One way that cells respond to oxidants is through the action of redox-regulated proteins. These proteins also play important roles in oxidant signaling and protein biogenesis events. The key sensors built into redox-regulated proteins are cysteines, which undergo reversible thiol oxidation in response to changes in the oxidation status of the cellular environment. In this review, we discuss three examples of redox-regulated proteins found in bacteria, mitochondria, and chloroplasts. These proteins use oxidation of their redox-sensitive cysteines to reversibly convert large structural domains into more disordered regions or vice versa. These massive structural rearrangements are directly implicated in the functions of these proteins.

► Disulfide bond formation promotes large-scale order ⇔ disorder transitions. ► Redox-mediated unfolding of Hsp33 leads to its activation as chaperone. ► Redox-mediated folding of COX17 impacts its function as copper chaperone. ► Redox-mediated folding of CP12 makes it the ‘on–off’ switch of the Calvin cycle. ► Developments in structural techniques show promise in revealing protein disorder.