Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Defining the hydrogen peroxide-dependent redoxome in human cells

ABSTRACT: Protein cysteinyl residues are the mediators of hydrogen peroxide (H2O2)-dependent redox signaling. However, site-specific mapping of the selectivity and dynamics of these redox reactions in cells poses a major analytical challenge. Here we describe a chemoproteomic platform to systematically and quantitatively analyze the reactivity of thousands of cysteines toward H2O2 in human cells. We identified >900 H2O2-sensitive cysteines, which are defined as the H2O2-dependent redoxome. Although redox sites associated with antioxidative and metabolic functions are consistent, most of the H2O2-dependent redoxome varies dramatically between different cells. Structural analyses reveal that H2O2-sensitive cysteines are less conserved than their redox-insensitive counterparts and display distinct sequence motifs, structural features, and potential for crosstalk with lysine modifications. Notably, our chemoproteomic platform also provides an opportunity to predict oxidation-triggered protein conformational changes. The data are freely accessible as a resource at http://redox.ncpsb.org/OXID/.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Hepatocyte, Epithelial Cell, Cell Culture

SUBMITTER: Jing Yang

LAB HEAD: Jing Yang

PROVIDER: PXD006657 | Pride | 2021-02-18

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	A0288_klc_20140708m_A431_Redoxome_H2O2_BR1_C1.pepXML	Pepxml
	A0288_klc_20140708m_A431_Redoxome_H2O2_BR1_C1.raw	Raw
	A0288_klc_20140708m_A431_Redoxome_H2O2_BR1_C2.pepXML	Pepxml
	A0288_klc_20140708m_A431_Redoxome_H2O2_BR1_C2.raw	Raw
	A0288_klc_20140708m_A431_Redoxome_H2O2_BR1_C3.pepXML	Pepxml

Items per page:

1 - 5 of 144

Similar Datasets

Systematic and quantitative assessment of hydrogen peroxide reactivity with cysteines across human proteomes

Project description:Protein cysteinyl residues are the mediators of hydrogen peroxide (H2O2)-dependent redox signaling. However, site-specific mapping of the selectivity and dynamics of these redox reactions in cells poses a major analytical challenge. Here we describe a chemoproteomic platform to systematically and quantitatively analyze the reactivity of thousands of cysteines toward H2O2 in human cells. We identified >900 H2O2-sensitive cysteines, which are defined as the H2O2-dependent redoxome. Although redox sites associated with antioxidative and metabolic functions are consistent, most of the H2O2-dependent redoxome varies dramatically between different cells. Structural analyses reveal that H2O2-sensitive cysteines are less conserved than their redox-insensitive counterparts and display distinct sequence motifs, structural features, and potential for crosstalk with lysine modifications. Notably, our chemoproteomic platform also provides an opportunity to predict oxidation-triggered protein conformational changes. The data are freely accessible as a resource at http://redox.ncpsb.org/OXID/.

2017-08-25 | PXD007153 | Pride

Multiplexed thiol reactivity profiling for target discovery of electrophilic natural products

Project description:Electrophilic groups, such as Michael acceptors, expoxides, are common motifs in natural products (NPs). Electrophilic NPs can act through covalent modification of cysteinyl thiols on functional proteins, and exhibit potent cytotoxicity and anti-inflammatory/cancer activities. Here we describe a new chemoproteomic strategy, termed multiplexed thiol reactivity profiling (MTRP), and its use in target discovery of electrophilic NPs. We demonstrate the utility of MTRP by identifying cellular targets of gambogic acid, an electrophilic NP that is currently under evaluation in clinical trials as anticancer agent. Moreover, MTRP enables simultaneous comparison of seven structurally diversified -unsaturated -lactones, which provides insights into the relative proteomic reactivity and target preference of diverse structural scaffolds coupled to a common electrophilic motif and reveals various potential druggable targets with liganded cysteines. We anticipate that this new method for thiol reactivity profiling in a multiplexed manner will find broad application in redox biology and drug discovery.

2017-10-12 | PXD007575 | Pride

Mining for protein S-sulfenylation in Arabidopsis uncovers redox-sensitive sites

Project description:Hydrogen peroxide (H2O2) is an important messenger molecule for diverse cellular processes. H2O2 oxidizes proteinaceous cysteinyl thiols to sulfenic acid, also known as S-sulfenylation, thereby affecting the protein conformation and functionality. Although many proteins have been identified as S-sulfenylation targets in plants, site-specific mapping and quantification remain largely unexplored. By means of peptide-centric chemoproteomics, 1,537 S-sulfenylated sites were mapped on more than 1,000 proteins in Arabidopsis thaliana cells. The H2O2 sensitivity was quantified of more than 70% of these endogenous oxidation events toward exogenous H2O2 stimulation. Proteins involved in RNA and metabolic processing were identified as hotspots for S-sulfenylation. Moreover, S-sulfenylation frequently occurred on cysteines located in catalytic sites of enzymes or on cysteines involved in metal binding, hinting at direct mode-of-actions for redox regulation. Comparison of human and Arabidopsis S-sulfenylation datasets provided 155 conserved S-sulfenylated cysteines, including Cys181 of the Arabidopsis MITOGEN-ACTIVATED PROTEIN KINASE4 (AtMAPK4) that corresponds to Cys161 in the human MAPK1, which is speculated to be a redox-regulatory site. Replacement of the noncatalytic Cys181 of the recombinant AtMAPK4 by the redox-insensitive serine decreased the protein kinase activity, emphasizing the importance of this noncatalytic cysteine. Altogether, we quantitatively mapped the S-sulfenylated cysteines in Arabidopsis plants under oxidative stress and delivered an unprecedented inventory for unraveling the precise role of these oxidized cysteines in plant redox signaling.

2019-09-16 | PXD013495 | Pride

4-Oxo-2-nonenal Adductions in Cells

Project description:4-Oxo-2-nonenal (ONE) derived from lipid peroxidation modifies nucleophiles and transduces redox signaling by its reactions with proteins. However, the molecular interactions between ONE and complex proteomes and their dynamics in situ remain largely unknown. Here we de-scribe a quantitative chemoproteomic analysis of protein adduction by ONE in cells, in which the cellular target profile of ONE is mimicked by its alkynyl surrogate. The analysis reveals four types of ONE-derived modifications in cells, including ketoamide and Schiff-base adducts to lysine, Michael adducts to cysteine, and a novel pyrrole adducts to cysteine. ONE-derived adducts co-localize and crosstalk with many histone marks and redox sensitive sites. All four types of modifications derived from ONE can be reversed site-specifically in cells. In summary, our study provides much-needed mechanistic insights into the cellular signaling and potential toxicities associated with this important lipid derived electrophile.

2017-08-25 | PXD007149 | Pride

Expression data from mouse limb tendon cells during development.

Project description:We have undertaken a screen of mouse limb tendon cells in order to identify molecular pathways involved in tendon development. Mouse limb tendon cells were isolated based on Scleraxis (Scx) expression at different stages of development: E11.5, E12.5 and E14.5 Microarray comparisons were carried out between tendon progenitor and differentiated stages. Forelimbs from E11.5, E12.5 and E14.5 Scx-GFP embryos were collected and dissociated with trypsin to obtain cell suspensions. Scx-positive tendon cells were isolated by FACS. RNA was extracted and Fragmented biotin-labelled cRNA samples were hybridized on Affymetrix Gene Chip Mouse Genome 430 2.0 arrays.

2014-01-18 | E-GEOD-54207 | biostudies-arrayexpress

Identification of heat stress-targets of translational control by large scale analysis of Arabidopsis trancriptome and translatome.

Project description:Heat stress is one of the most prominent and deleterious environmental threads affecting plant growth and development. Upon high temperatures, plants launch specialized gene expression programs that promote stress protection and survival. These programs involve global and specific changes at the transcriptional and translational levels. However the coordination of these processes and their specific role in the establishment of the heat stress response is not fully elucidated. In this report, we have carried out a genome-wide analysis to simultaneously monitor the individual changes in the transcriptional and translational mRNA levels of Arabidopsis thaliana seedlings after the exposure to a heat shock stress. Our results demonstrated that, superimposed to transcription, translation exerts a wide but dual regulation of gene expression. For the majority of mRNAs, translation is severely repressed, causing a decreased of 50% of the association of the bulk of mRNAs to polysomes. However, some relevant mRNAs involved in different aspects of homeostasis maintenance follow a differential pattern of translation. Analysis of the sequence of the differentially translated mRNAs unravels that some features, like the 5M-BM-4UTR G+C content and the cDNA length, may take part in the discrimination mechanisms for mRNA polysome loading. Among the differential translated genes stand out master regulators of the stress response, highlighting the main role of translation in the early establishment of physiological response of plants to elevated temperatures. In total 8 ATH1 Affymetrix GeneChips were hybridized with all combinations of two factors: total mRNA/polysome-bound-RNA; 22M-BM-:C/38M-BM-:C. Two biological replicates per sample type were performed.

2014-01-22 | E-GEOD-44053 | biostudies-arrayexpress

pChem_benchmarking_dataset_QTRP_diff_species

Project description:Data sets are used for benchmarking, pChem, a modification-centric, blind-search tool to provide a streamlined pipeline for unbiased assessing of the performance of chemoproteomic probes. Data were produced from the IPM-based QTRP (quantitative thiol reactivity profiling) applications in various species, including Arabidopsis thaliana, Escherichia coli, Homo sapiens, Rattus norvegicus, Drosophila melanogaster, Caenorhabditis elegans, Psedomonas syringae, and Mus musculus. IPM is a clickable thiol reactive reagent with the iodoacetamide warhead.

2024-09-24 | PXD027767 | Pride

pChem_benchmarking_dataset_redoxome

Project description:Data sets are used for benchmarking, pChem, a modification-centric, blind-search tool to provide a streamlined pipeline for unbiased assessing of the performance of chemoproteomic probes. Data were produced from the redoxome profiling experiments using oxoform-specific probes as indicated, including SOH probes (DYn-2, BTD, WYneC/O/N) and SO2H probe (DiaAlk). All these probes contain a clickable alkyne handle.

2023-02-27 | PXD027764 | Pride

pChem_benchmarking_dataset_QTRP_diff_ratios

Project description:Data sets are used for benchmarking, pChem, a modification-centric, blind-search tool to provide a streamlined pipeline for unbiased assessing of the performance of chemoproteomic probes. Data were produced from the IPM-based QTRP (quantitative thiol reactivity profiling) experiments where light and heavy IPM-tagged samples mixed in different ratios (L/H = 1:10, 1:5, 1:2, 1:1, 2:1, 5:1 and 10:1). IPM is a clickable thiol reactive reagent with the iodoacetamide warhead.

2022-12-16 | PXD027762 | Pride

pChem_benchmarking_dataset_QTRP_diff_instruments

Project description:Data sets are used for benchmarking, pChem, a modification-centric, blind-search tool to provide a streamlined pipeline for unbiased assessing of the performance of chemoproteomic probes. The IPM-based QTRP (quantitative thiol reactivity profiling) data sets were recorded on different LC-MS/MS instruments from three vendors. IPM is a clickable thiol reactive reagent with the iodoacetamide warhead.

2022-12-16 | PXD027758 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data