Modification of cysteine residues by cyclopentenone prostaglandins: Interplay with redox regulation of protein function

2013 ◽  
Vol 33 (2) ◽  
pp. 110-125 ◽  
Author(s):  
Clara L. Oeste ◽  
Dolores Pérez-Sala
Keyword(s):  
Protein Function ◽  
Redox Regulation ◽  
Cysteine Residues ◽  
Cyclopentenone Prostaglandins

scholarly journals Role of the cysteine residues in Arabidopsis thaliana cyclophilin CYP20-3 in peptidyl-prolyl cis–trans isomerase and redox-related functions

2006 ◽  
Vol 401 (1) ◽  
pp. 287-297 ◽  
Author(s):  
Miriam Laxa ◽  
Janine König ◽  
Karl-Josef Dietz ◽  
Andrea Kandlbinder
Keyword(s):  
Conformational Changes ◽  
Protein Function ◽  
Redox Regulation ◽  
Catalytic Efficiency ◽  
Structural Rearrangement ◽  
Disulfide Bridge ◽  
Cysteine Residues ◽  
Active Centre ◽  
Independent Functions

Cyps (cyclophilins) are ubiquitous proteins of the immunophilin superfamily with proposed functions in protein folding, protein degradation, stress response and signal transduction. Conserved cysteine residues further suggest a role in redox regulation. In order to get insight into the conformational change mechanism and functional properties of the chloroplast-located CYP20-3, site-directed mutagenized cysteine→serine variants were generated and analysed for enzymatic and conformational properties under reducing and oxidizing conditions. Compared with the wild-type form, elimination of three out of the four cysteine residues decreased the catalytic efficiency of PPI (peptidyl-prolyl cis–trans isomerase) activity of the reduced CYP20-3, indicating a regulatory role of dithiol–disulfide transitions in protein function. Oxidation was accompanied by conformational changes with a predominant role in the structural rearrangement of the disulfide bridge formed between Cys54 and Cys171. The rather negative Em (midpoint redox potential) of −319 mV places CYP20-3 into the redox hierarchy of the chloroplast, suggesting the activation of CYP20-3 in the light under conditions of limited acceptor availability for photosynthesis as realized under environmental stress. Chloroplast Prx (peroxiredoxins) were identified as interacting partners of CYP20-3 in a DNA-protection assay. A catalytic role in the reduction of 2-Cys PrxA and 2-Cys PrxB was assigned to Cys129 and Cys171. In addition, it was shown that the isomerization and disulfide-reduction activities are two independent functions of CYP20-3 that both are regulated by the redox state of its active centre.

Pinpointing cysteine oxidation sites by high-resolution proteomics reveals a mechanism of redox-dependent inhibition of human STING

2021 ◽  
Vol 14 (680) ◽  
pp. eaaw4673
Author(s):  
Natalia Zamorano Cuervo ◽  
Audray Fortin ◽  
Elise Caron ◽  
Stéfany Chartier ◽  
Nathalie Grandvaux
Keyword(s):  
Posttranslational Modifications ◽  
Protein Function ◽  
Disulfide Bonds ◽  
Redox Regulation ◽  
Mass Spectrometry Analysis ◽  
Type I ◽  
Cysteine Oxidation ◽  
Spectrometry Analysis ◽  
Host Interactions ◽  
In Cells

Protein function is regulated by posttranslational modifications (PTMs), among which reversible oxidation of cysteine residues has emerged as a key regulatory mechanism of cellular responses. Given the redox regulation of virus-host interactions, the identification of oxidized cysteine sites in cells is essential to understand the underlying mechanisms involved. Here, we present a proteome-wide identification of reversibly oxidized cysteine sites in oxidant-treated cells using a maleimide-based bioswitch method coupled to mass spectrometry analysis. We identified 2720 unique oxidized cysteine sites within 1473 proteins with distinct abundances, locations, and functions. Oxidized cysteine sites were found in numerous signaling pathways, many relevant to virus-host interactions. We focused on the oxidation of STING, the central adaptor of the innate immune type I interferon pathway, which is stimulated in response to the detection of cytosolic DNA by cGAS. We demonstrated the reversible oxidation of Cys148 and Cys206 of STING in cells. Molecular analyses led us to establish a model in which Cys148 oxidation is constitutive, whereas Cys206 oxidation is inducible by oxidative stress or by the natural ligand of STING, 2′3′-cGAMP. Our data suggest that the oxidation of Cys206 prevented hyperactivation of STING by causing a conformational change associated with the formation of inactive polymers containing intermolecular disulfide bonds. This finding should aid the design of therapies targeting STING that are relevant to autoinflammatory disorders, immunotherapies, and vaccines.

Plastidic P2 glucose-6P dehydrogenase from poplar is modulated by thioredoxin m-type: Distinct roles of cysteine residues in redox regulation and NADPH inhibition

Plant Science ◽  
2016 ◽  
Vol 252 ◽  
pp. 257-266 ◽  
Author(s):  
Manuela Cardi ◽  
Mirko Zaffagnini ◽  
Alessia De Lillo ◽  
Daniela Castiglia ◽  
Kamel Chibani ◽  
...  
Keyword(s):  
Redox Regulation ◽  
Cysteine Residues

scholarly journals S-sulfhydration as a cellular redox regulation

2016 ◽  
Vol 36 (2) ◽  
Author(s):  
Małgorzata Iciek ◽  
Danuta Kowalczyk-Pachel ◽  
Anna Bilska-Wilkosz ◽  
Inga Kwiecień ◽  
Magdalena Górny ◽  
...  
Keyword(s):  
Protein Function ◽  
Redox Regulation ◽  
Biological Significance ◽  
Redox Signaling ◽  
Sulfur Species ◽  
Cellular Redox ◽  
Reactive Sulfur Species

This review is focused on formation and biological significance of hydropersulfides, i.e. S-sulfhydration process. Biogenesis and properties of reactive sulfur species and their role in redox signaling are presented. The effect of S-sulfhydration on protein function is discussed.

PGluS: prediction of protein S-glutathionylation sites with multiple features and analysis

2015 ◽  
Vol 11 (3) ◽  
pp. 923-929 ◽  
Author(s):  
Xiaowei Zhao ◽  
Qiao Ning ◽  
Meiyu Ai ◽  
Haiting Chai ◽  
Minghao Yin
Keyword(s):  
Protein Stability ◽  
Redox Regulation ◽  
Protein S ◽  
Cysteine Residues ◽  
Post Translational Modification ◽  
Multiple Features ◽  
Mixed Disulfides

S-Glutathionylation is a reversible protein post-translational modification, which generates mixed disulfides between glutathione (GSH) and cysteine residues, playing an important role in regulating protein stability, activity, and redox regulation.

Redox-dependent stability of the γ-glutamylcysteine synthetase enzyme of Escherichia coli: a novel means of redox regulation

2013 ◽  
Vol 449 (3) ◽  
pp. 783-794 ◽  
Author(s):  
Shailesh Kumar ◽  
Neha Kasturia ◽  
Amit Sharma ◽  
Manish Datt ◽  
Anand K. Bachhawat
Keyword(s):  
Escherichia Coli ◽  
Disulfide Bond ◽  
Redox Regulation ◽  
Catalytic Efficiency ◽  
Reduced Form ◽  
Cysteine Residues ◽  
Glutathione Biosynthesis ◽  
Glutamylcysteine Synthetase ◽  
The Stability

Glutathione is a thiol-containing tripeptide that plays important roles in redox-related processes. The first step in glutathione biosynthesis is catalysed by γ-GCS (γ-glutamylcysteine synthetase). The crystal structure of Escherichia coli γ-GCS has revealed the presence of a disulfide bond. As the disulfide-bonding cysteine residues Cys372 and Cys395 are not well conserved among γ-GCS enzymes in this lineage, we have initiated a biochemical genetic strategy to investigate the functional importance of these and other cysteine residues. In a cysteine-free γ-GCS that was non-functional, suppressor analysis yielded combinations of cysteine and aromatic residues at the position of the disulfide bond, and one mutant that lacked any cysteine residues. Kinetic analysis of the wild-type and mutant enzymes revealed that the disulfide bond was not involved in determining the affinity of the enzyme towards its substrate, but had an important role in determining the stability of the protein, and its catalytic efficiency. We show that in vivo the γ-GCS enzyme can also exist in a reduced form and that the mutants lacking the disulfide bond show a decreased half-life. These results demonstrate a novel means of regulation of γ-GCS by the redox environment that works by an alteration in its stability.

Thiol switches in redox regulation of chloroplasts: balancing redox state, metabolism and oxidative stress

2015 ◽  
Vol 396 (5) ◽  
pp. 483-494 ◽  
Author(s):  
Karl-Josef Dietz ◽  
Rüdiger Hell
Keyword(s):  
Protein Function ◽  
Regulatory Network ◽  
Redox Regulation ◽  
Oxidation Reactions ◽  
Macromolecular Assemblies ◽  
Major Player ◽  
Thiol Redox ◽  
Conditional Function ◽  
And Function ◽  
Powerful Mechanism

Abstract In photosynthesizing chloroplasts, rapidly changing energy input, intermediate generation of strong reductants as well as oxidants and multiple participating physicochemical processes and pathways, call for efficient regulation. Coupling redox information to protein function via thiol modifications offers a powerful mechanism to activate, down-regulate and coordinate interdependent processes. Efficient thiol switching of target proteins involves the thiol-disulfide redox regulatory network, which is highly elaborated in chloroplasts. This review addresses the features of this network. Its conditional function depends on specificity of reduction and oxidation reactions and pathways, thiol redox buffering, but also formation of heterogeneous milieus by microdomains, metabolite gradients and macromolecular assemblies. One major player is glutathione. Its synthesis and function is under feedback redox control. The number of thiol-controlled processes and involved thiol switched proteins is steadily increasing, e.g., in tetrapyrrole biosynthesis, plastid transcription and plastid translation. Thus chloroplasts utilize an intricate and versatile redox regulatory network for intraorganellar and retrograde communication.

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