Global profiling of distinct cysteine redox forms reveals wide-ranging redox regulation in C. elegans

Abstract

Post-translational changes in the redox state of cysteine residues can rapidly and reversibly alter protein functions, thereby modulating biological processes. The nematode C. elegans is an ideal model organism for studying cysteine-mediated redox signaling at a network level. Here we present a comprehensive, quantitative, and site-specific profile of the intrinsic reactivity of the cysteinome in wild-type C. elegans. We also describe a global characterization of the C. elegans redoxome in which we measured changes in three major cysteine redox forms after H2O2 treatment. Our data revealed redox-sensitive events in translation, growth signaling, and stress response pathways, and identified redox-regulated cysteines that are important for signaling through the p38 MAP kinase (MAPK) pathway. Our in-depth proteomic dataset provides a molecular basis for understanding redox signaling in vivo, and will serve as a valuable and rich resource for the field of redox biology.

ATF-4 and hydrogen sulfide signalling mediate longevity from inhibition of translation or mTORC1

“…It was particularly intriguing that the ATF-4/CTH-2 pathway, which boosts H2S formation and PSSH levels, was required for lifespan extension from mTORC1 suppression. This ATF-4/H2S-induced posttranslational shift in PSSH levels could influence many biological functions, including the activity of redox-regulated signalling pathways 35,37 , making it of interest to elucidate how these modifications mediate the downstream effects of mTORC1 signalling.…”

“…Redox modification at reactive cysteine residues is critical in growth signalling and other mechanisms 36 , and in C. elegans thousands of redox-regulated cysteine residues are present in proteins that are involved in translation regulation, lipid and carbohydrate metabolism, stress signalling, and other fundamental biological processes 37 . Under oxidising conditions, these thiols are readily converted to sulfenic acids (-SOH), which is a reversible and in many cases regulatory modification that can proceed to irreversible and potentially damaging oxidized forms (-SO2H, -SO3H) (Fig.…”

pChem: a modification-centric assessment tool for the performance of chemoproteomic probes

“…Raw data files previously generated by using the IPM-based QTRP method are available from ProteomeXchange (PXD027762 for evaluating quantification accuracy 4 ; PXD027767 for profiling the cysteinome in Drosophila melanogaster 68 , Caenorhabditis elegans 43 , Psedomonas syringae 69 , and Mus musculus 70 ). Raw analyses of chemoproteomic data sets based on oxoform-specific probes (i.e., DYn-2, BTD, WYnes and DiaAlk) have been described previously and are available now from ProteomeXchange (PXD027764) 12-13, 42, 49-50 .…”

Parallel evaluation of nucleophilic and electrophilic chemical probes for sulfenic acid: Reactivity, selectivity and biocompatibility

“…Most sulfenic acids are transient intermediates to other OxiPTMs, primarily disulfide bridges that confer protein structural stability, or in some cases redox-active disulfides with regulatory functions [ 7 ]. Overall, profiling protein sulfenic acid modification has paved the way for elucidation of redox-based mechanisms in various organisms [ [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] ].…”