Methionine Sulfoxide Reductases of Archaea

Methionine sulfoxide reductases are found in all domains of life and are important in reversing the oxidative damage of the free and protein forms of methionine, a sulfur containing amino acid particularly sensitive to reactive oxygen species (ROS). Archaea are microbes of a domain of life distinct from bacteria and eukaryotes. Archaea are well known for their ability to withstand harsh environmental conditions that range from habitats of high ROS, such as hypersaline lakes of intense ultraviolet (UV) radiation and desiccation, to hydrothermal vents of low concentrations of dissolved oxygen at high temperature. Recent evidence reveals the methionine sulfoxide reductases of archaea function not only in the reduction of methionine sulfoxide but also in the ubiquitin-like modification of protein targets during oxidative stress, an association that appears evolutionarily conserved in eukaryotes. Here is reviewed methionine sulfoxide reductases and their distribution and function in archaea.

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Involvement of the MetO/Msr System in Two Acer Species That Display Contrasting Characteristics during Germination

International Journal of Molecular Sciences ◽

10.3390/ijms21239197 ◽

2020 ◽

Vol 21 (23) ◽

pp. 9197

Author(s):

Natalia Wojciechowska ◽

Shirin Alipour ◽

Ewelina Stolarska ◽

Karolina Bilska ◽

Pascal Rey ◽

...

Keyword(s):

Hydroxyl Radicals ◽

Superoxide Anion ◽

Redox Homeostasis ◽

Methionine Sulfoxide ◽

Redox System ◽

Oxygen Species ◽

Embryonic Axes ◽

Methionine Sulfoxide Reductases ◽

Germination Process ◽

Norway Maple

The levels of methionine sulfoxide (MetO) and the abundances of methionine sulfoxide reductases (Msrs) were reported as important for the desiccation tolerance of Acer seeds. To determine whether the MetO/Msrs system is related to reactive oxygen species (ROS) and involved in the regulation of germination in orthodox and recalcitrant seeds, Norway maple and sycamore were investigated. Changes in water content, MetO content, the abundance of MsrB1 and MsrB2 in relation to ROS content and the activity of reductases depending on nicotinamide adenine dinucleotides were monitored. Acer seeds differed in germination speed—substantially higher in sycamore—hydration dynamics, levels of hydrogen peroxide, superoxide anion radicals (O2•−) and hydroxyl radicals (•OH), which exhibited peaks at different stages of germination. The MetO level dynamically changed, particularly in sycamore embryonic axes, where it was positively correlated with the levels of O2•− and the abundance of MsrB1 and negatively with the levels of •OH and the abundance of MsrB2. The MsrB2 abundance increased upon sycamore germination; in contrast, it markedly decreased in Norway maple. We propose that the ROS–MetO–Msr redox system, allowing balanced Met redox homeostasis, participates in the germination process in sycamore, which is characterized by a much higher speed compared to Norway maple.

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Redox-mediated regulation of a labile, evolutionarily conserved cross-β structure formed by the TDP43 low complexity domain

10.1101/2019.12.24.885962 ◽

2019 ◽

Author(s):

Yi Lin ◽

Xiaoming Zhou ◽

Masato Kato ◽

Daifei Liu ◽

Sina Ghaemmaghami ◽

...

Keyword(s):

Rna Binding ◽

Thioredoxin Reductase ◽

Methionine Sulfoxide ◽

Low Complexity ◽

Methionine Sulfoxide Reductase ◽

Methionine Residue ◽

Low Concentrations ◽

Evolutionarily Conserved ◽

Methionine Residues ◽

Self Association

SummaryAn evolutionarily conserved low complexity (LC) domain is found within a 152 residue segment localized to the carboxyl-terminal region of the TDP43 RNA-binding protein. This TDP43 LC domain contains ten conserved methionine residues. Self-association of this domain leads to the formation of liquid-like droplets composed of labile, cross-β polymers. Exposure of polymers to low concentrations of H2O2 leads to a phenomenon of droplet melting that can be reversed upon exposure of the oxidized protein to the MsrA and MsrB methionine sulfoxide reductase enzymes, thioredoxin, thioredoxin reductase and NADPH. Morphological features of the cross-β polymers were revealed by a method of H2O2-mediated footprinting. Similar TDP43 LC domain footprints were observed in highly polymerized, hydrogel samples, liquid-like droplet samples, and living cells. The ability of H2O2 to impede cross-β polymerization was abrogated by a prominent ALS-causing mutation that changes methionine residue 337 to valine. These observations offer potentially useful insight into the biological role of TDP43 in facilitating synapse-localized translation, as well as aberrant aggregation of the protein in neurodegenerative disease.

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In Vivo Effects of Methionine Sulfoxide Reductase Deficiency in Drosophila melanogaster

Antioxidants ◽

10.3390/antiox7110155 ◽

2018 ◽

Vol 7 (11) ◽

pp. 155 ◽

Cited By ~ 1

Author(s):

Lindsay Bruce ◽

Diana Singkornrat ◽

Kelsey Wilson ◽

William Hausman ◽

Kelli Robbins ◽

...

Keyword(s):

Methionine Sulfoxide ◽

Methionine Sulfoxide Reductase ◽

Model Organisms ◽

Methionine Sulfoxide Reductase A ◽

Methionine Sulfoxide Reductases ◽

Methionine Residues ◽

Oxidation Of Methionine ◽

And Function ◽

In Vivo Effects

The deleterious alteration of protein structure and function due to the oxidation of methionine residues has been studied extensively in age-associated neurodegenerative disorders such as Alzheimer’s and Parkinson’s Disease. Methionine sulfoxide reductases (MSR) have three well-characterized biological functions. The most commonly studied function is the reduction of oxidized methionine residues back into functional methionine thus, often restoring biological function to proteins. Previous studies have successfully overexpressed and silenced MSR activity in numerous model organisms correlating its activity to longevity and oxidative stress. In the present study, we have characterized in vivo effects of MSR deficiency in Drosophila. Interestingly, we found no significant phenotype in animals lacking either methionine sulfoxide reductase A (MSRA) or methionine sulfoxide reductase B (MSRB). However, Drosophila lacking any known MSR activity exhibited a prolonged larval third instar development and a shortened lifespan. These data suggest an essential role of MSR in key biological processes.

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The Oxidized Protein Repair Enzymes Methionine Sulfoxide Reductases and Their Roles in Protecting against Oxidative Stress, in Ageing and in Regulating Protein Function

Antioxidants ◽

10.3390/antiox7120191 ◽

2018 ◽

Vol 7 (12) ◽

pp. 191 ◽

Cited By ~ 9

Author(s):

Sofia Lourenço dos Santos ◽

Isabelle Petropoulos ◽

Bertrand Friguet

Keyword(s):

Oxidative Stress ◽

Reactive Oxygen Species ◽

Protein Function ◽

Methionine Sulfoxide ◽

Methionine Sulfoxide Reductase ◽

Methionine Oxidation ◽

Oxygen Species ◽

Sulfenic Acid ◽

Protein Repair ◽

Methionine Sulfoxide Reductases

Cysteine and methionine residues are the amino acids most sensitive to oxidation by reactive oxygen species. However, in contrast to other amino acids, certain cysteine and methionine oxidation products can be reduced within proteins by dedicated enzymatic repair systems. Oxidation of cysteine first results in either the formation of a disulfide bridge or a sulfenic acid. Sulfenic acid can be converted to disulfide or sulfenamide or further oxidized to sulfinic acid. Disulfide can be easily reversed by different enzymatic systems such as the thioredoxin/thioredoxin reductase and the glutaredoxin/glutathione/glutathione reductase systems. Methionine side chains can also be oxidized by reactive oxygen species. Methionine oxidation, by the addition of an extra oxygen atom, leads to the generation of methionine sulfoxide. Enzymatically catalyzed reduction of methionine sulfoxide is achieved by either methionine sulfoxide reductase A or methionine sulfoxide reductase B, also referred as to the methionine sulfoxide reductases system. This oxidized protein repair system is further described in this review article in terms of its discovery and biologically relevant characteristics, and its important physiological roles in protecting against oxidative stress, in ageing and in regulating protein function.

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Methionine Redox Homeostasis in Protein Quality Control

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.665492 ◽

2021 ◽

Vol 8 ◽

Author(s):

Laurent Aussel ◽

Benjamin Ezraty

Keyword(s):

Oxidative Stress ◽

Quality Control ◽

Protein Function ◽

Protein Quality ◽

Redox Homeostasis ◽

Protein Quality Control ◽

Methionine Sulfoxide ◽

Methionine Sulfoxide Reductases ◽

Methionine Residues ◽

And Function

Bacteria live in different environments and are subject to a wide variety of fluctuating conditions. During evolution, they acquired sophisticated systems dedicated to maintaining protein structure and function, especially during oxidative stress. Under such conditions, methionine residues are converted into methionine sulfoxide (Met-O) which can alter protein function. In this review, we focus on the role in protein quality control of methionine sulfoxide reductases (Msr) which repair oxidatively protein-bound Met-O. We discuss our current understanding of the importance of Msr systems in rescuing protein function under oxidative stress and their ability to work in coordination with chaperone networks. Moreover, we highlight that bacterial chaperones, like GroEL or SurA, are also targeted by oxidative stress and under the surveillance of Msr. Therefore, integration of methionine redox homeostasis in protein quality control during oxidative stress gives a complete picture of this bacterial adaptive mechanism.

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Methionine Sulfoxide Reduction in Mammals: Characterization of Methionine-R-Sulfoxide Reductases

Molecular Biology of the Cell ◽

10.1091/mbc.e03-08-0629 ◽

2004 ◽

Vol 15 (3) ◽

pp. 1055-1064 ◽

Cited By ~ 218

Author(s):

Hwa-Young Kim ◽

Vadim N. Gladyshev

Keyword(s):

Reductase Activity ◽

Methionine Sulfoxide ◽

Oxygen Species ◽

High Affinity ◽

Methionine Sulfoxide Reductases ◽

Specific Manner ◽

Methionine Residues ◽

Cellular Compartments ◽

Human And Mouse

Methionine residues in proteins are susceptible to oxidation by reactive oxygen species, but can be repaired via reduction of the resulting methionine sulfoxides by methionine-S-sulfoxide reductase (MsrA) and methionine-R-sulfoxide reductase (MsrB). However, the identity of all methionine sulfoxide reductases involved, their cellular locations and relative contributions to the overall pathway are poorly understood. Here, we describe a methionine-R-sulfoxide reduction system in mammals, in which two MsrB homologues were previously described. We found that human and mouse genomes possess three MsrB genes and characterized their protein products, designated MsrB1, MsrB2, and MsrB3. MsrB1 (Selenoprotein R) was present in the cytosol and nucleus and exhibited the highest methionine-R-sulfoxide reductase activity because of the presence of selenocysteine (Sec) in its active site. Other mammalian MsrBs contained cysteine in place of Sec and were less catalytically efficient. MsrB2 (CBS-1) resided in mitochondria. It had high affinity for methionine-R-sulfoxide, but was inhibited by higher concentrations of the substrate. The human MsrB3 gene gave rise to two protein forms, MsrB3A and MsrB3B. These were generated by alternative splicing that introduced contrasting N-terminal and C-terminal signals, such that MsrB3A was targeted to the endoplasmic reticulum and MsrB3B to mitochondria. We found that only mitochondrial forms of mammalian MsrBs (MsrB2 and MsrB3B) could compensate for MsrA and MsrB deficiency in yeast. All mammalian MsrBs belonged to a group of zinc-containing proteins. The multiplicity of MsrBs contrasted with the presence of a single mammalian MsrA gene as well as with the occurrence of single MsrA and MsrB genes in yeast, fruit flies, and nematodes. The data suggested that different cellular compartments in mammals maintain a system for repair of oxidized methionine residues and that this function is tuned in enzyme- and stereo-specific manner.

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The Antioxidant Enzyme Methionine Sulfoxide Reductase A (MsrA) Interacts with Jab1/CSN5 and Regulates Its Function

Antioxidants ◽

10.3390/antiox9050452 ◽

2020 ◽

Vol 9 (5) ◽

pp. 452 ◽

Cited By ~ 1

Author(s):

Beichen Jiang ◽

Zachary Adams ◽

Shannon Moonah ◽

Honglian Shi ◽

Julie Maupin-Furlow ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Survival ◽

Kinase Inhibitor ◽

Methionine Sulfoxide ◽

Methionine Sulfoxide Reductase ◽

Methionine Sulfoxide Reductase A ◽

Cyclin Dependent Kinase Inhibitor ◽

Evolutionarily Conserved ◽

And Function ◽

Positive Effect

Methionine sulfoxide (MetO) is an oxidative posttranslational modification that primarily occurs under oxidative stress conditions, leading to alteration of protein structure and function. This modification is regulated by MetO reduction through the evolutionarily conserved methionine sulfoxide reductase (Msr) system. The Msr type A enzyme (MsrA) plays an important role as a cellular antioxidant and promotes cell survival. The ubiquitin- (Ub) like neddylation pathway, which is controlled by the c-Jun activation domain-binding protein-1 (Jab1), also affects cell survival. Jab1 negatively regulates expression of the cell cycle inhibitor cyclin-dependent kinase inhibitor 1B (P27) through binding and targeting P27 for ubiquitination and degradation. Here we report the finding that MsrA interacts with Jab1 and enhances Jab1′s deneddylase activity (removal of Nedd8). In turn, an increase is observed in the level of deneddylated Cullin-1 (Cul-1, a component of E3 Ub ligase complexes). Furthermore, the action of MsrA increases the binding affinity of Jab1 to P27, while MsrA ablation causes a dramatic increase in P27 expression. Thus, an interaction between MsrA and Jab1 is proposed to have a positive effect on the function of Jab1 and to serve as a means to regulate cellular resistance to oxidative stress and to enhance cell survival.

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Methionine sulfoxide reductases: selenoprotein forms and roles in antioxidant protein repair in mammals

Biochemical Journal ◽

10.1042/bj20070929 ◽

2007 ◽

Vol 407 (3) ◽

pp. 321-329 ◽

Cited By ~ 152

Author(s):

Hwa-Young Kim ◽

Vadim N. Gladyshev

Keyword(s):

Catalytic Properties ◽

Methionine Sulfoxide ◽

Protein Repair ◽

Disease Evolution ◽

Repair Enzymes ◽

Antioxidant Protein ◽

Current Review ◽

Methionine Sulfoxide Reductases ◽

Methionine Residues ◽

And Function

Msrs (methionine sulfoxide reductases), MsrA and MsrB, are repair enzymes that reduce methionine sulfoxide residues in oxidatively damaged proteins to methionine residues in a stereospecific manner. These enzymes protect cells from oxidative stress and have been implicated in delaying the aging process and progression of neurodegenerative diseases. In recent years, significant efforts have been made to explore the catalytic properties and physiological functions of these enzymes. In the current review, we present recent progress in this area, with the focus on mammalian MsrA and MsrBs including their roles in disease, evolution and function of selenoprotein forms of MsrA and MsrB, and the biochemistry of these enzymes.

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