The cysteine proteome

Abstract

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, metallation, 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 discriminate 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.

Redox homeostasis and age‐related deficits in neuromuscular integrity and function

“…Recent application of novel redox proteomic approaches has identified and quantified reversible and irreversible modifications of susceptible Cys residues of redox‐sensitive proteins expressed in skeletal muscle 81, 151, 182. An extended coverage of these goes beyond the scope of this review; for a detailed description, see Refs [183, 184, 185]. Briefly, the type of redox modification on Cys residues depends on the concentration and species of RONS as well as the amino acids surrounding the Cys residue.…”

Progress in understanding the molecular oxygen paradox – function of mitochondrial reactive oxygen species in cell signaling

“…Oxidative eustress refers to a physiological oxidative challenge where H 2 O 2 is utilized in adaptive or regulatory signaling (Sies et al, 2017). In this scenario, cellular ROS like H 2 O 2 are utilized to oxidize redox switches on proteins to modulate genomic, transcriptional, and metabolic programs in response to changes in the exposome (Go et al, 2015). Thus, oxidative eustress, also known as the redox interface, allows for cellular adaptation in response to changes in the intracellular and extracellular environment (Jones, 2015).…”

Exposure Memory and Lung Regeneration

“…All aerobic life depends on oxidation-reduction reactions for energy supply, so oxidation cannot be equated with [23], redox signaling of growth factor [vascular endothelial growth factor, platelet-derived growth factor, epidermal growth factor, fibroblast growth factor]-dependent cell proliferation) have been studied in detail (24)(25)(26). Redox mechanisms also provide an organizational structure for cells through the redox proteome (27,28). This process has been described in terms of "redox sensing," defined as mechanisms orthogonal to redox signaling, which control cell organization, trafficking, and functional integration (29).…”

“…In development and regeneration of the lung, O 2 is an oxidant that has signaling activity through HIF-1a (35,36). Many other biologic oxidants have been described, and these oxidants function through specific signaling events as well as less specifically in maintaining networks of redox-sensitive elements (27). More precise use of terminology can be expected to aid in delineating relevant mechanisms for lung regeneration.…”

“…The central organization structure is linked to the bioenergetics systems through mitochondrial H 2 O 2 production and H 2 O 2 generation by NADPH oxidases (Nox) (44,45). Relatively slow, kinetically controlled oxidation of Cys (46,47) in transcription factors, actin cytoskeleton, mRNA and microRNA (miRNA) processing and trafficking machinery, molecular chaperones and docking proteins, translation and apoptosis machinery, and enzymes for glycolysis, lipid, and protein metabolism, is countered by thioredoxin-or GSH-dependent reduction, each linked to NADPH, to maintain stable steady states (27,28). The broad impact of oxidative stress on the redox proteome structure has been delineated in lung fibroblasts for low, environmental levels of cadmium exposure (48).…”