The cysteine proteome

The cysteine (Cys) proteome is a major component of the adaptive interface between the genome and the exposome. The thiol moiety of Cys undergoes a range of biologic modifications enabling biological switching of structure and reactivity. These biological modifications include sulfenylation and disulfide formation, formation of higher oxidation states, S-nitrosylation, persulfidation, metalation, and other modifications. Extensive knowledge about these systems and their compartmentalization now provides a foundation to develop advanced integrative models of Cys proteome regulation. In particular, detailed understanding of redox signaling pathways and sensing networks is becoming available to allow the discrimination of network structures. This research focuses attention on the need for atlases of Cys modifications to develop systems biology models. Such atlases will be especially useful for integrative studies linking the Cys proteome to imaging and other omics platforms, providing a basis for improved redox-based therapeutics. Thus, a framework is emerging to place the Cys proteome as a complement to the quantitative proteome in the omics continuum connecting the genome to the exposome. [Display omitted] •The cysteine proteome provides an interface for an organism to sense and adapt to its environment, including resources, such as food and O2, and threats, such as infection and toxicants.•Functional switching of protein structure and reactivity occurs through purposeful sulfenylation, disulfide formation, oxidation to higher oxidation states, S-nitrosylation, persulfidation, metalation, and other modifications.•Systematic mapping of cysteine proteome reactivities and modifications will support integrated systems biology models connecting cell signaling and other complex functions; this mapping will enable new therapeutic approaches targeting redox networks.