Molecular Evidence of Adenosine Deaminase Linking Adenosine A2A Receptor and CD26 Proteins DOI Creative Commons
Estefanía Moreno,

Júlia Canet,

Eduard Gracia

et al.

Frontiers in Pharmacology, Journal Year: 2018, Volume and Issue: 9

Published: Feb. 15, 2018

Adenosine is an endogenous purine nucleoside that acts in all living systems as a homeostatic network regulator through many pathways, which are adenosine receptor (AR)-dependent and -independent. From metabolic point of view, deaminase (ADA) essential protein the regulation total intracellular extracellular tissue. In addition to its cytosolic localization, ADA also expressed ecto-enzyme on surface different cells. Dipeptidyl peptidase IV (CD26) some ARs act binding proteins for humans. Since CD26 interact with at opposite sites, we have investigated if can function cell-to-cell communication molecule by bridging anchoring molecules A2AR present surfaces interacting By combining site-directed mutagenesis amino acids involved modification bioluminescence resonance energy transfer (BRET) technique allows detection interactions between two cell populations low steric hindrance (NanoBRET), show direct evidence specific formation trimeric complexes CD26-ADA-A2AR involving dynamic mass redistribution assays ligand experiments, demonstrate A2AR-NanoLuc fusion functional. The existence this ternary complex good agreement hypothesis could bridge T-cells (expressing CD26) dendritic cells A2AR). This new ecto-ADA that, being single chain protein, it has been considered example moonlighting because performs more than one functional role (as catalyst, costimulator, allosteric modulator connector) without partitioning these functions subunits.

Language: Английский

Mycoplasma pneumoniae from the Respiratory Tract and Beyond DOI Open Access
Ken B. Waites, Li Xiao, Yang Liu

et al.

Clinical Microbiology Reviews, Journal Year: 2017, Volume and Issue: 30(3), P. 747 - 809

Published: May 25, 2017

SUMMARY Mycoplasma pneumoniae is an important cause of respiratory tract infections in children as well adults that can range severity from mild to life-threatening. Over the past several years there has been much new information published concerning caused by this organism. New molecular-based tests for M. detection are now commercially available United States, and advances molecular typing systems have enhanced understanding epidemiology infections. More strains had their entire genome sequences published, providing additional insights into pathogenic mechanisms. Clinically significant acquired macrolide resistance emerged worldwide complicating treatment. In vitro susceptibility testing methods standardized, drugs may be effective against organism undergoing development. This review focuses on many developments occurred over enhance our microbe, which among smallest bacterial pathogens but one great clinical importance.

Language: Английский

Citations

637

Conformationally adaptive therapeutic peptides for diseases caused by intrinsically disordered proteins (IDPs). New paradigm for drug discovery: Target the target, not the arrow DOI Creative Commons
Jacques Fantini, Fodil Azzaz, Coralie Di Scala

et al.

Pharmacology & Therapeutics, Journal Year: 2025, Volume and Issue: unknown, P. 108797 - 108797

Published: Jan. 1, 2025

The traditional model of protein structure determined by the amino acid sequence is today seriously challenged fact that approximately half human proteome made up proteins do not have a stable 3D structure, either partially or in totality. These proteins, called intrinsically disordered (IDPs), are involved numerous physiological functions and associated with severe pathologies, e.g. Alzheimer, Parkinson, Creutzfeldt-Jakob, amyotrophic lateral sclerosis (ALS), type 2 diabetes. Targeting these challenging for two reasons: i) we need to preserve their functions, ii) drug design molecular docking possible due lack reliable starting conditions. Faced this challenge, solutions proposed artificial intelligence (AI) such as AlphaFold clearly unsuitable. Instead, suggest an innovative approach consisting mimicking, short synthetic peptides, conformational flexibility IDPs. which call adaptive derived from domains IDPs become structured after interacting ligand. Adaptive peptides designed aim selectively antagonizing harmful effects IDPs, without targeting them directly but through selected ligands, affecting properties. This"target target, arrow" strategy promised open new route discovery currently undruggable proteins.

Language: Английский

Citations

4

New intracellular activities of matrix metalloproteinases shine in the moonlight DOI Creative Commons
Parker G. Jobin, Georgina S. Butler, Christopher M. Overall

et al.

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Journal Year: 2017, Volume and Issue: 1864(11), P. 2043 - 2055

Published: May 16, 2017

Language: Английский

Citations

162

Moonlighting Proteins DOI
Nadia D. Singh, Needhi Bhalla

Annual Review of Genetics, Journal Year: 2020, Volume and Issue: 54(1), P. 265 - 285

Published: Sept. 1, 2020

The single gene, protein, function hypothesis is increasingly becoming obsolete. Numerous studies have demonstrated that individual proteins can moonlight, meaning they multiple functions based on their cellular or developmental context. In this review, we discuss moonlighting proteins, highlighting the biological pathways where phenomenon may be particularly relevant. addition, combine genetic, cell biological, and evolutionary perspectives so better understand how, when, why take roles.

Language: Английский

Citations

122

Why study moonlighting proteins? DOI Creative Commons
Constance J. Jeffery

Frontiers in Genetics, Journal Year: 2015, Volume and Issue: 6

Published: June 19, 2015

OPINION article Front. Genet., 19 June 2015Sec. Computational Genomics https://doi.org/10.3389/fgene.2015.00211

Language: Английский

Citations

120

FFPred 3: feature-based function prediction for all Gene Ontology domains DOI Creative Commons
Domenico Cozzetto,

Federico Minneci,

Hannah Currant

et al.

Scientific Reports, Journal Year: 2016, Volume and Issue: 6(1)

Published: Aug. 26, 2016

Abstract Predicting protein function has been a major goal of bioinformatics for several decades, and it gained fresh momentum thanks to recent community-wide blind tests aimed at benchmarking available tools on genomic scale. Sequence-based predictors, especially those performing homology-based transfers, remain the most popular but increasing understanding their limitations stimulated development complementary approaches, which mostly exploit machine learning. Here we present FFPred 3, is intended assigning Gene Ontology terms human chains, when homology with characterized proteins can provide little aid. Predictions are made by scanning input sequences against an array Support Vector Machines (SVMs), each examining relationship between biophysical attributes describing secondary structure, transmembrane helices, intrinsically disordered regions, signal peptides other motifs. This update features larger SVM library that extends its coverage cellular component sub-ontology first time, prompted establishment dedicated evaluation category within Critical Assessment Functional Annotation. The effectiveness this approach demonstrated through experiments, usefulness illustrated analysing potential functional consequences alternative splicing in patterns biological features.

Language: Английский

Citations

120

The role of transmitter diffusion and flow versus extracellular vesicles in volume transmission in the brain neural–glial networks DOI Open Access
Dasiel O. Borroto‐Escuela,

Luigi F. Agnati,

Karl Bechter

et al.

Philosophical Transactions of the Royal Society B Biological Sciences, Journal Year: 2015, Volume and Issue: 370(1672), P. 20140183 - 20140183

Published: May 26, 2015

Two major types of intercellular communication are found in the central nervous system (CNS), namely wiring transmission (point-to-point communication, prototype being synaptic with axons and terminals) volume (VT; extracellular fluid cerebrospinal (CSF)) involving large numbers cells CNS. Volume become integrated inter alia through ability their chemical signals to activate different receptor protomers heteroreceptor complexes located synaptically or extrasynaptically plasma membrane. The demonstration dopamine (DA) serotonin (5-HT) fluorescence around DA 5-HT nerve cell bodies Falck-Hillarp formaldehyde method after treatment amphetamine chlorimipramine, respectively, gave first indications existence VT brain, at least soma level. There exist forms VT. Early studies on only involved spread including diffusion flow soluble biological signals, especially transmitters modulators, a called extrasynaptic (short distance) long distance (paraaxonal paravascular CSF pathways) Also, vesicle type was demonstrated. exosomes (endosome-derived vesicles) appear be vesicular carriers for but larger microvesicles also participate. Both mainly originate soma-dendritic They can transfer lipids proteins, receptors, Rab GTPases, tetraspanins, cholesterol, sphingolipids ceramide. Within them there subsets mRNAs non-coding regulatory microRNAs. At membrane, sets dynamic postsynaptic (built up physically interacting receptors proteins) G protein-coupled autoreceptors, ion channel tyrosine kinases hypothesized molecular basis learning memory. terminals, presynaptic postulated undergo plastic changes maintain pattern multiple transmitter release reflecting firing learned by

Language: Английский

Citations

119

Unfolding the Mysteries of Protein Metamorphosis DOI Creative Commons
Acacia F. Dishman, Brian F. Volkman

ACS Chemical Biology, Journal Year: 2018, Volume and Issue: 13(6), P. 1438 - 1446

Published: May 22, 2018

Since the proposal of Anfinsen's thermodynamic hypothesis in 1963, our understanding protein folding and dynamics has gained significant appreciation its nuance complexity. Intrinsically disordered proteins, chameleonic sequences, morpheeins, metamorphic proteins have broadened paradigm. Here, we discuss noncanonical patterns, with an emphasis on review known that occur naturally been engineered laboratory. Finally, research areas surrounding are primed for future exploration, including evolution, drug discovery, quest previously unrecognized metamorphs. As enter age where capable complex bioinformatic searches de novo design, to search design own metamorphs act as targeted, switchable drugs; biosensors; more.

Language: Английский

Citations

106

Extracellular Vesicle-Associated Transitory Cell Wall Components and Their Impact on the Interaction of Fungi with Host Cells DOI Creative Commons
Leonardo Nimrichter,

Marcio M. de Souza,

Maurizio Del Poeta

et al.

Frontiers in Microbiology, Journal Year: 2016, Volume and Issue: 7

Published: July 8, 2016

Classic cell wall components of fungi comprise the polysaccharides glucans and chitin, in association with glycoproteins pigments. During last decade, however, system biology approaches clearly demonstrated that composition fungal walls include atypical molecules historically associated intracellular or membrane locations. Elucidation mechanisms by which many are exported to extracellular space suggested these transitorily located wall. The presence vesicles (EVs) at culture supernatants distinct pathogenic species a highly functional mechanism molecular export organisms. Thus, passage EVs through suggests remarkable diversity and, consequently, potentially variable influence on host antifungal response. On basis information derived from proteomic characterization yeasts Cryptoccocus neoformans Candida albicans dimorphic Histoplasma capsulatum Paracoccidioides brasiliensis, our manuscript is focused clear view much more complex than previously thought.

Language: Английский

Citations

88

The versatile functions of OsALDH2B1 provide a genic basis for growth–defense trade-offs in rice DOI Open Access
Yinggen Ke, Meng Yuan, Hongbo Liu

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2020, Volume and Issue: 117(7), P. 3867 - 3873

Published: Feb. 5, 2020

Significance Crops’ defense activation often causes growth inhibition and yield reduction, which is referred to as trade-offs between defense. In this study, we identified a gene, OsALDH2B1 , that functions master regulator of the growth–defense trade-off in rice. The findings provide an example for genic basis plants may also have important implication crop genetic improvement by exploring modulating these components achieve balance high disease resistance.

Language: Английский

Citations

78