Incidence and physiological relevance of protein thiol switches

2015 ◽  
Vol 396 (5) ◽  
pp. 389-399 ◽  
Author(s):  
Lars I. Leichert ◽  
Tobias P. Dick
Keyword(s):  
Hydrogen Peroxide ◽  
Model Organisms ◽  
Cysteine Residues ◽  
Host Proteins ◽  
Protein Thiol ◽  
Redox Active ◽  
Physiological Relevance ◽  
Significant Interest ◽  
Thiol Switch ◽  
Redox Switches

Abstract A few small-molecule oxidants, most notably hydrogen peroxide, can act as messengers in signal transduction. They trigger so-called ‘thiol switches’, cysteine residues that are reversibly oxidized to transiently change the functional properties of their host proteins. The proteome-wide identification of functionally relevant ‘thiol switches’ is of significant interest. Unfortunately, prediction of redox-active cysteine residues on the basis of surface accessibility and other computational parameters appears to be of limited use. Proteomic thiol labeling approaches remain the most reliable strategy to discover new thiol switches in a hypothesis-free manner. We discuss if and how genomic knock-in strategies can help establish the physiological relevance of a ‘thiol switch’ on the organismal level. We conclude that surprisingly few attempts have been made to thoroughly verify the physiological relevance of thiol-based redox switches in mammalian model organisms.

Thiol switches in mitochondria: operation and physiological relevance

2015 ◽  
Vol 396 (5) ◽  
pp. 465-482 ◽  
Author(s):  
Jan Riemer ◽  
Markus Schwarzländer ◽  
Marcus Conrad ◽  
Johannes M. Herrmann
Keyword(s):  
Reactive Oxygen Species ◽  
Hydrogen Peroxide ◽  
Redox Conditions ◽  
Cysteine Residues ◽  
Mitochondrial Enzymes ◽  
Intermembrane Space ◽  
Oxygen Species ◽  
Redox Systems ◽  
Physiological Relevance ◽  
The Matrix

Abstract Mitochondria are a major source of reactive oxygen species (ROS) in the cell, particularly of superoxide and hydrogen peroxide. A number of dedicated enzymes regulate the conversion and consumption of superoxide and hydrogen peroxide in the intermembrane space and the matrix of mitochondria. Nevertheless, hydrogen peroxide can also interact with many other mitochondrial enzymes, particularly those with reactive cysteine residues, modulating their reactivity in accordance with changes in redox conditions. In this review we will describe the general redox systems in mitochondria of animals, fungi and plants and discuss potential target proteins that were proposed to contain regulatory thiol switches.

scholarly journals Actions of redox-active compound resveratrol under hydrogen peroxide insult in C6 astroglial cells

2010 ◽  
Vol 24 (3) ◽  
pp. 916-920 ◽  
Author(s):  
André Quincozes-Santos ◽  
Ana Cristina Andreazza ◽  
Carlos-Alberto Gonçalves ◽  
Carmem Gottfried
Keyword(s):  
Hydrogen Peroxide ◽  
Active Compound ◽  
Astroglial Cells ◽  
Redox Active ◽  
C6 Astroglial Cells

scholarly journals Hepatitis C Virus RNA-Dependent RNA Polymerase Is Regulated by Cysteine S-Glutathionylation

2019 ◽  
Vol 2019 ◽  
pp. 1-11
Author(s):  
Marina K. Kukhanova ◽  
Vera L. Tunitskaya ◽  
Olga A. Smirnova ◽  
Olga A. Khomich ◽  
Natalia F. Zakirova ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Recombinant Protein ◽  
Rna Polymerase ◽  
Reducing Agents ◽  
Cysteine Residues ◽  
Rdrp Activity ◽  
Rna Dependent Rna Polymerase ◽  
Redox Switches ◽  
Ns5b Protein

Hepatitis C virus (HCV) triggers massive production of reactive oxygen species (ROS) and affects expression of genes encoding ROS-scavenging enzymes. Multiple lines of evidence show that levels of ROS production contribute to the development of various virus-associated pathologies. However, investigation of HCV redox biology so far remained in the paradigm of oxidative stress, whereas no attention was given to the identification of redox switches among viral proteins. Here, we report that one of such redox switches is the NS5B protein that exhibits RNA-dependent RNA polymerase (RdRp) activity. Treatment of the recombinant protein with reducing agents significantly increases its enzymatic activity. Moreover, we show that the NS5B protein is subjected to S-glutathionylation that affects cysteine residues 89, 140, 170, 223, 274, 521, and either 279 or 295. Substitution of these cysteines except C89 and C223 with serine residues led to the reduction of the RdRp activity of the recombinant protein in a primer-dependent assay. The recombinant protein with a C279S mutation was almost inactive in vitro and could not be activated with reducing agents. In contrast, cysteine substitutions in the NS5B region in the context of a subgenomic replicon displayed opposite effects: most of the mutations enhanced HCV replication. This difference may be explained by the deleterious effect of oxidation of NS5B cysteine residues in liver cells and by the protective role of S-glutathionylation. Based on these data, redox-sensitive posttranslational modifications of HCV NS5B and other proteins merit a more detailed investigation and analysis of their role(s) in the virus life cycle and associated pathogenesis.

scholarly journals Discovery of a Redox Thiol Switch: Implications for Cellular Energy Metabolism

2020 ◽  
Vol 19 (5) ◽  
pp. 852-870 ◽  
Author(s):  
Xing-Huang Gao ◽  
Ling Li ◽  
Marc Parisien ◽  
Jing Wu ◽  
Ilya Bederman ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Energy Metabolism ◽  
Pancreatic Beta Cells ◽  
Large Scale ◽  
Protein S ◽  
Cysteine Residues ◽  
Cellular Energy ◽  
Cellular Energy Metabolism ◽  
Proteomics Approach ◽  
Thiol Switch

The redox-based modifications of cysteine residues in proteins regulate their function in many biological processes. The gas molecule H2S has been shown to persulfidate redox sensitive cysteine residues resulting in an H2S-modified proteome known as the sulfhydrome. Tandem Mass Tags (TMT) multiplexing strategies for large-scale proteomic analyses have become increasingly prevalent in detecting cysteine modifications. Here we developed a TMT-based proteomics approach for selectively trapping and tagging cysteine persulfides in the cellular proteomes. We revealed the natural protein sulfhydrome of two human cell lines, and identified insulin as a novel substrate in pancreatic beta cells. Moreover, we showed that under oxidative stress conditions, increased H2S can target enzymes involved in energy metabolism by switching specific cysteine modifications to persulfides. Specifically, we discovered a Redox Thiol Switch, from protein S-glutathioinylation to S-persulfidation (RTSGS). We propose that the RTSGS from S-glutathioinylation to S-persulfidation is a potential mechanism to fine tune cellular energy metabolism in response to different levels of oxidative stress.

scholarly journals Suppressing hydrogen peroxide generation to achieve oxygen-insensitivity of a [NiFe] hydrogenase in redox active films

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Huaiguang Li ◽  
Ute Münchberg ◽  
Alaa A. Oughli ◽  
Darren Buesen ◽  
Wolfgang Lubitz ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Redox Active ◽  
Hydrogen Peroxide Generation

Protein thiol depletion and the killing of cultured hepatocytes by hydrogen peroxide

1989 ◽  
Vol 38 (21) ◽  
pp. 3797-3805 ◽  
Author(s):  
Marlene E. Kyle ◽  
Dai Nakae ◽  
Isao Sakaida ◽  
Ada Serroni ◽  
John L. Farber
Keyword(s):  
Hydrogen Peroxide ◽  
Cultured Hepatocytes ◽  
Protein Thiol

scholarly journals Novel Oxidative Modifications in Redox-Active Cysteine Residues

2010 ◽  
Vol 10 (3) ◽  
pp. M110.000513 ◽  
Author(s):  
Jaeho Jeong ◽  
Yongsik Jung ◽  
Seungjin Na ◽  
Jihye Jeong ◽  
Eunsun Lee ◽  
...  
Keyword(s):  
Cysteine Residues ◽  
Redox Active ◽  
Oxidative Modifications ◽  
Redox Active Cysteine
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