Thiol-based posttranslational modifications in parasites

Cysteine residues of proteins participate in the catalysis of biochemical reactions, are crucial for redox reactions, and influence protein structure by the formation of disulfide bonds. Covalent posttranslational modifications (PTMs) of cysteine residues are important mediators of redox regulation and signaling by coupling protein activity to the cellular redox state, and moreover influence stability, function, and localization of proteins. A diverse group of protozoan and metazoan parasites are a major cause of diseases in humans, such as malaria, African trypanosomiasis, leishmaniasis, toxoplasmosis, filariasis, and schistosomiasis.Human parasites undergo dramatic morphological and metabolic changes while they pass complex life cycles and adapt to changing environments in host and vector. These processes are in part regulated by PTMs of parasitic proteins. In human parasites, posttranslational cysteine modifications are involved in crucial cellular events such as signal transduction (S-glutathionylation and S-nitrosylation), redox regulation of proteins (S-glutathionylation and S-nitrosylation), protein trafficking and subcellular localization (palmitoylation and prenylation), as well as invasion into and egress from host cells (palmitoylation). This review focuses on the occurrence and mechanisms of these cysteine modifications in parasites.Studies on cysteine modifications in human parasites are so far largely based on in vitro experiments.The in vivo regulation of cysteine modifications and their role in parasite development will be of great interest in order to understand redox signaling in parasites.