The STIM-Orai Pathway: Regulation of STIM and Orai by Thiol Modifications.

Cysteines are among the least abundant amino acids found in proteins. Due to their unique nucleophilic thiol group, they are able to undergo a broad range of chemical modifications besides their known role in disulfide formation, such as S-sulfenylation (-SOH), S-sulfinylation (-SO(2)H), S-sufonylation (-SO(3)H), S-glutathionylation (-SSG), and S-sulfhydration (-SSH), among others. These posttranslational modifications can be irreversible and act as transitional modifiers or as reversible on-off switches for the function of proteins. Disturbances of the redox homeostasis, for example, in situations of increased oxidative stress, can contribute to a range of diseases. Because Ca2+ signaling mediated by store-operated calcium entry (SOCE) is involved in a plethora of cellular responses, the cross-talk between reactive oxygen species (ROS) and Ca2+ is critical for homeostatic control. Identification of calcium regulatory protein targets of thiol redox modifications is needed to understand their role in biology and disease.