scholarly journals Prediction of thioredoxin and glutaredoxin target proteins by identifying reversibly oxidized cysteinyl residues

2010 ◽  
Vol 7 (3) ◽  
pp. 208-218 ◽  
Author(s):  
Hang-mao Lee ◽  
Karl Josef Dietz ◽  
Ralf Hofestädt
Keyword(s):  
Regulatory Network ◽  
Structural Model ◽  
Regulatory Protein ◽  
Recall Rate ◽  
Plant Mitochondrion ◽  
Network Construction ◽  
Target Proteins ◽  
The Public ◽  
Protein Functions ◽  
Redox Transitions

Summary A significant part of cellular proteins undergo reversible thiol-dependent redox transitions which often control or switch protein functions. Thioredoxins and glutaredoxins constitute two key players in this redox regulatory protein network. Both interact with various categories of proteins containing reversibly oxidized cysteinyl residues. The identification of thioredoxin/glutaredoxin target proteins is a critical step in constructing the redox regulatory network of cells or subcellular compartments. Due to the scarcity of thioredoxin/glutaredoxin target protein records in the public database, a tool called Reversibly Oxidized Cysteine Detector (ROCD) is implemented here to identify potential thioredoxin/glutaredoxin target proteins computationally, so that the in silico construction of redox regulatory network may become feasible. ROCD was tested on 46 thioredoxin target proteins in plant mitochondrion, and the recall rate was 66.7% when 50% sequence identity was chosen for structural model selection. ROCD will be used to predict the thioredoxin/glutaredoxin target proteins in human liver mitochondrion for our redox regulatory network construction project. The ROCD will be developed further to provide prediction with more reliability and incorporated into biological network visualization tools as a node prediction component. This work will advance the capability of traditional database- or text mining-based method in the network construction.

A Web without a Center

2018 ◽  
Author(s):  
Peter Knaack
Keyword(s):  
Regulatory Network ◽  
Financial Stability ◽  
Public Governance ◽  
The Public ◽  
Otc Derivatives ◽  
Unilateral Action ◽  
Regulatory Cooperation ◽  
Private And Public ◽  
Legal Barriers ◽  
Global Data

G20 leaders vowed to collect and share OTC derivatives trade data so that regulators can obtain a global picture of market and risk evolution. This chapter employs a network perspective to explain why they have failed to meet this commitment to date. It examines three networks: the OTC derivatives market itself, and those of its private and public governance. The analysis shows that the Financial Stability Board (FSB), the public supervisory entity, struggles to establish itself at the center of the global regulatory network. It failed to act as a first mover in setting global trade identification standards (legal entity identifiers), and it has not been able to establish a core of global data warehouses. This is largely the result of unilateral action by FSB members. In particular, legislators in member countries have undermined FSB-led efforts by refusing to remove legal barriers to transnational regulatory cooperation and, in some instances, by erecting new ones.

scholarly journals Paramyxovirus V Proteins Interact with the RIG-I/TRIM25 Regulatory Complex and Inhibit RIG-I Signaling

2018 ◽  
Vol 92 (6) ◽  
Author(s):  
Maria T. Sánchez-Aparicio ◽  
Leighland J. Feinman ◽  
Adolfo García-Sastre ◽  
Megan L. Shaw
Keyword(s):  
Signaling Pathway ◽  
Measles Virus ◽  
Sendai Virus ◽  
Regulatory Protein ◽  
Nipah Virus ◽  
Antiviral Signaling ◽  
V Protein ◽  
Protein Functions ◽  
Regulatory Complex ◽  
Mitochondrial Antiviral Signaling

ABSTRACT Paramyxovirus V proteins are known antagonists of the RIG-I-like receptor (RLR)-mediated interferon induction pathway, interacting with and inhibiting the RLR MDA5. We report interactions between the Nipah virus V protein and both RIG-I regulatory protein TRIM25 and RIG-I. We also observed interactions between these host proteins and the V proteins of measles virus, Sendai virus, and parainfluenza virus. These interactions are mediated by the conserved C-terminal domain of the V protein, which binds to the tandem caspase activation and recruitment domains (CARDs) of RIG-I (the region of TRIM25 ubiquitination) and to the SPRY domain of TRIM25, which mediates TRIM25 interaction with the RIG-I CARDs. Furthermore, we show that V interaction with TRIM25 and RIG-I prevents TRIM25-mediated ubiquitination of RIG-I and disrupts downstream RIG-I signaling to the mitochondrial antiviral signaling protein. This is a novel mechanism for innate immune inhibition by paramyxovirus V proteins, distinct from other known V protein functions such as MDA5 and STAT1 antagonism. IMPORTANCE The host RIG-I signaling pathway is a key early obstacle to paramyxovirus infection, as it results in rapid induction of an antiviral response. This study shows that paramyxovirus V proteins interact with and inhibit the activation of RIG-I, thereby interrupting the antiviral signaling pathway and facilitating virus replication.

scholarly journals Computational simulation of the reactive oxygen species and redox network in the regulation of chloroplast metabolism

2019 ◽  
Author(s):  
Melanie Gerken ◽  
Sergej Kakorin ◽  
Kamel Chibani ◽  
Karl-Josef Dietz
Keyword(s):  
Reactive Oxygen Species ◽  
Regulatory Network ◽  
Electron Flow ◽  
Computational Simulation ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Animal Cells ◽  
Unknown Parameters ◽  
Target Proteins ◽  
Thiol Redox

AbstractCells contain a thiol redox regulatory network to coordinate metabolic and developmental activities with exogenous and endogenous cues. This network controls the redox state and activity of many target proteins. Electrons are fed into the network from metabolism and reach the target proteins via redox transmitters such as thioredoxin (TRX) and NADPH-dependent thioredoxin reductases (NTR). Electrons are drained from the network by reactive oxygen species (ROS) through thiol peroxidases, e.g., peroxiredoxins (PRX). Mathematical modeling promises access to quantitative understanding of the network function and was implemented for the photosynthesizing chloroplast by using published kinetic parameters combined with fitting to known biochemical data. Two networks were assembled, namely the ferredoxin (FDX), FDX-dependent TRX reductase (FTR), TRX, fructose-1,6-bisphosphatase pathway with 2-cysteine PRX/ROS as oxidant, and separately the FDX, FDX-dependent NADP reductase (FNR), NADPH, NTRC-pathway for 2-CysPRX reduction. Combining both modules allowed drawing several important conclusions of network performance. The resting H2O2 concentration was estimated to be about 30 nM in the chloroplast stroma. The electron flow to metabolism exceeds that into thiol regulation of FBPase more than 7000-fold under physiological conditions. The electron flow from NTRC to 2-CysPRX is about 5.46-times more efficient than that from TRX-f1 to 2-CysPRX. Under severe stress (30 μM H2O2) the ratio of electron flow to the thiol network relative to metabolism sinks to 1:251 whereas the ratio of electron flow from NTRC to 2-CysPRX and TRX-f1 to 2-CysPRX rises up to 1:80. Thus, the simulation provides clues on experimentally inaccessible parameters and describes the functional state of the chloroplast thiol regulatory network.Authors summaryThe state of the thiol redox regulatory network is a fundamental feature of all cells and determines metabolic and developmental processes. However, only some parameters are quantifiable in experiments. This paper establishes partial mathematical models which enable simulation of electron flows through the regulatory system. This in turn allows for estimating rates and states of components of the network and to tentatively address previously unknown parameters such as the resting hydrogen peroxide levels or the expenditure of reductive power for regulation relative to metabolism. The establishment of such models for simulating the performance and dynamics of the redox regulatory network is of significance not only for photosynthesis but also, e.g., in bacterial and animal cells exposed to environmental stress or pathological disorders.

scholarly journals FALCON2: a web server for high-quality prediction of protein tertiary structures

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Lupeng Kong ◽  
Fusong Ju ◽  
Haicang Zhang ◽  
Shiwei Sun ◽  
Dongbo Bu
Keyword(s):  
Protein Structure ◽  
Ab Initio ◽  
Protein Structure Prediction ◽  
Structure Prediction ◽  
Web Server ◽  
High Quality ◽  
Tertiary Structures ◽  
Target Proteins ◽  
High Quality Protein ◽  
Protein Functions

Abstract Background Accurate prediction of protein tertiary structures is highly desired as the knowledge of protein structures provides invaluable insights into protein functions. We have designed two approaches to protein structure prediction, including a template-based modeling approach (called ProALIGN) and an ab initio prediction approach (called ProFOLD). Briefly speaking, ProALIGN aligns a target protein with templates through exploiting the patterns of context-specific alignment motifs and then builds the final structure with reference to the homologous templates. In contrast, ProFOLD uses an end-to-end neural network to estimate inter-residue distances of target proteins and builds structures that satisfy these distance constraints. These two approaches emphasize different characteristics of target proteins: ProALIGN exploits structure information of homologous templates of target proteins while ProFOLD exploits the co-evolutionary information carried by homologous protein sequences. Recent progress has shown that the combination of template-based modeling and ab initio approaches is promising. Results In the study, we present FALCON2, a web server that integrates ProALIGN and ProFOLD to provide high-quality protein structure prediction service. For a target protein, FALCON2 executes ProALIGN and ProFOLD simultaneously to predict possible structures and selects the most likely one as the final prediction result. We evaluated FALCON2 on widely-used benchmarks, including 104 CASP13 (the 13th Critical Assessment of protein Structure Prediction) targets and 91 CASP14 targets. In-depth examination suggests that when high-quality templates are available, ProALIGN is superior to ProFOLD and in other cases, ProFOLD shows better performance. By integrating these two approaches with different emphasis, FALCON2 server outperforms the two individual approaches and also achieves state-of-the-art performance compared with existing approaches. Conclusions By integrating template-based modeling and ab initio approaches, FALCON2 provides an easy-to-use and high-quality protein structure prediction service for the community and we expect it to enable insights into a deep understanding of protein functions.

scholarly journals Pathways to workplace innovation and career satisfaction in the public service

2018 ◽  
Vol 26 (5) ◽  
pp. 890-914 ◽  
Author(s):  
Warit Wipulanusat ◽  
Kriengsak Panuwatwanich ◽  
Rodney Anthony Stewart
Keyword(s):  
Public Service ◽  
Structural Equation ◽  
Structural Model ◽  
Career Satisfaction ◽  
Innovation Process ◽  
Mediation Effects ◽  
Content Type ◽  
Professional Career ◽  
The Public ◽  
Workplace Innovation

Purpose The purpose of this paper is to study the influence of two climates for innovation constructs, namely, leadership and organisational culture, on workplace innovation and career satisfaction. Design/methodology/approach This study used structural equation modelling to test the data from 3,125 engineering professionals in the Australian Public Service (APS). Findings The structural model indicated that leadership for innovation and ambidextrous culture for innovation influenced workplace innovation which, in turn, improved career satisfaction. Moreover, modelling revealed a significant relationship between ambidextrous culture for innovation and career satisfaction. This study also investigated mediation effects and revealed both simple and sequential mediation paths in the model. It was found that improving workplace innovation and career satisfaction through recognition of an engineer’s contribution to their agency would assist in retaining and advancing in-house engineering expertise. Practical implications The structural model could be used to address current shortages of engineering professionals in the Commonwealth of Australia departments. The findings emphasise the importance of Commonwealth departments providing opportunities for their engineers to engage in creative and innovative projects which enhance their professional career. Originality/value This study fills the gap in the innovation literature by exploring the relationships through which socio-psychological factors affect workplace innovation and career satisfaction on the innovation process for engineering professionals in the APS.

scholarly journals Social and Political Attitudes of Moscow Students on the Background of the All-Russia and Regional Youth Studies

2020 ◽  
Vol 9 (9) ◽  
pp. 153
Author(s):  
Tatiana Litvinova ◽  
Olga Vershinina ◽  
Gennady Moskvitin
Keyword(s):  
Structural Model ◽  
Political Attitudes ◽  
Personal Values ◽  
Age Factors ◽  
Political Activity ◽  
Youth Studies ◽  
The Public ◽  
Gender And Age ◽  
Four Levels ◽  
The Public Sphere

The purpose of the article is to study the socio-political attitudes of Moscow students, which determine their life strategies in the public sphere. An empirical basis for the study was the sociological survey of students of three universities in Moscow (n = 768). The questionnaire was partially based on Milton Rokeach’s terminal personal values indicators and the methodology of studying political culture of Gabriel Almond and Sidney Verba, adapted to a Russian context. The survey data operationalization let us represent a structural model of socio-political attitudes of Moscow students, which consists of indicators of four levels: value, emotional, cognitive, and strategic. The results showed that students in Moscow share the values and patriotic feelings of the elder generations. The influence of gender and age factors was most pronounced on the level of personal values. Despite of the field of their study, students in Moscow can be described as quite energetic and optimistic young citizens, equally family and career oriented with not a high interest in politics and weak political activity. Authors discussed their main findings with the results of previously obtained all-Russian and regional youth studies.

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