ADP-Ribosylation and Antiviral Resistance in Plants DOI Creative Commons
Nadezhda Spechenkova, Natalia O. Kalinina, С. К. Завриев

et al.

Viruses, Journal Year: 2023, Volume and Issue: 15(1), P. 241 - 241

Published: Jan. 14, 2023

ADP-ribosylation (ADPRylation) is a versatile posttranslational modification in eukaryotic cells which involved the regulation of wide range key biological processes, including DNA repair, cell signalling, programmed death, growth and development responses to biotic abiotic stresses. Members poly(ADP-ribosyl) polymerase (PARP) family play central role process ADPRylation. Protein targets can be modified by adding either single ADP-ribose moiety (mono(ADP-ribosyl)ation; MARylation), catalysed mono(ADP-ribosyl) transferases (MARTs or PARP "monoenzymes"), may decorated with chains multiple moieties (PARylation), via activities "polyenzymes". Studies have revealed crosstalk between PARylation (and lesser extent, MARylation) processes plants plant-virus interactions, suggesting that these tight links represent novel factor regulating plant antiviral immunity. From this perspective, we go through literature linking PARylation-associated other pathways controlling virus resistance. Once unraveled, serve as basis innovative strategies improve crop resistance viruses under challenging environmental conditions could mitigate yield losses.

Language: Английский

ADP-ribosylation from molecular mechanisms to therapeutic implications DOI Creative Commons
Marcin J. Suskiewicz, Evgeniia Prokhorova, J.G.M. Rack

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(21), P. 4475 - 4495

Published: Oct. 1, 2023

ADP-ribosylation is a ubiquitous modification of biomolecules, including proteins and nucleic acids, that regulates various cellular functions in all kingdoms life. The recent emergence new technologies to study has reshaped our understanding the molecular mechanisms govern establishment, removal, recognition this modification, as well its impact on organismal function. These advances have also revealed intricate involvement human physiology pathology enormous potential their manipulation holds for therapy. In review, we present state-of-the-art findings covering work structural biology, biochemistry, cell clinical aspects ADP-ribosylation.

Language: Английский

Citations

80
Molecular basis for the reversible ADP-ribosylation of guanosine bases DOI Creative Commons
M. Schuller,

Roberto Raggiaschi,

Petra Mikolčević

et al.

Molecular Cell, Journal Year: 2023, Volume and Issue: 83(13), P. 2303 - 2315.e6

Published: June 29, 2023

Modification of nucleic acids by ADP-ribosylation is catalyzed various ADP-ribosyltransferases, including the DarT enzyme. The latter part bacterial toxin-antitoxin (TA) system DarTG, which was shown to provide control DNA replication and growth as well protection against bacteriophages. Two subfamilies have been identified, DarTG1 DarTG2, are distinguished their associated antitoxins. While DarTG2 catalyzes reversible thymidine bases employing a macrodomain antitoxin, activity biochemical function its NADAR domain, yet unknown. Using structural approaches, we show that DarT1-NADAR TA for guanosine bases. DarT1 evolved ability link ADP-ribose guanine amino group, specifically hydrolyzed NADAR. We de-ADP-ribosylation also conserved among eukaryotic non-DarT-associated members, indicating wide distribution modifications beyond DarTG systems.

Language: Английский

Citations

29
Phages reconstitute NAD+ to counter bacterial immunity DOI
Ilya А. Osterman,

Hadar Samra,

François Rousset

et al.

Nature, Journal Year: 2024, Volume and Issue: 634(8036), P. 1160 - 1167

Published: Sept. 25, 2024

Language: Английский

Citations

17
Retron-Eco1 assembles NAD+-hydrolyzing filaments that provide immunity against bacteriophages DOI
Arturo Carabias, Sarah Camara-Wilpert, Mario Rodríguez Mestre

et al.

Molecular Cell, Journal Year: 2024, Volume and Issue: 84(11), P. 2185 - 2202.e12

Published: May 23, 2024

Language: Английский

Citations

13
Serine ADP-ribosylation in Drosophila provides insights into the evolution of reversible ADP-ribosylation signalling DOI Creative Commons
Pietro Fontana, Sara C. Buch-Larsen, Osamu Suyari

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: June 2, 2023

Abstract In the mammalian DNA damage response, ADP-ribosylation signalling is of crucial importance to mark sites as well recruit and regulate repairs factors. Specifically, PARP1:HPF1 complex recognises damaged catalyses formation serine-linked marks (mono-Ser-ADPr), which are extended into ADP-ribose polymers (poly-Ser-ADPr) by PARP1 alone. Poly-Ser-ADPr reversed PARG, while terminal mono-Ser-ADPr removed ARH3. Despite its significance apparent evolutionary conservation, little known about in non-mammalian Animalia . The presence HPF1, but absence ARH3, some insect genomes, including Drosophila species, raises questions regarding existence reversal serine-ADP-ribosylation these species. Here we show quantitative proteomics that Ser-ADPr major form response melanogaster dependent on d Parp1: Hpf1 complex. Moreover, our structural biochemical investigations uncover mechanism removal Parg. Collectively, data reveal PARP:HPF1-mediated a defining feature DDR striking conservation within this kingdom suggests organisms carry only core set ADP-ribosyl metabolising enzymes, such , valuable model study physiological role signalling.

Language: Английский

Citations

19
Anti-viral defense by an ADP-ribosyltransferase that targets mRNA to block translation DOI Creative Commons
Christopher N. Vassallo, Christopher R. Doering, Michael T. Laub

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 24, 2024

Abstract Host-pathogen conflicts are crucibles of molecular innovation. Selection for immunity to pathogens has driven the evolution sophisticated mechanisms throughout biology, including in bacteria that must evade their viral predators known as bacteriophages. Here, we characterize a widely distributed anti-phage defense system, CmdTAC, provides robust against infection by T-even family phages. Our results support model which CmdC detects sensing capsid proteins, ultimately leading activation toxic ADP-ribosyltransferase effector protein, CmdT. We show newly synthesized protein triggers dissociation chaperone from CmdTAC complex, destabilization and degradation antitoxin CmdA, with consequent liberation CmdT ADP-ribosyltransferase. Strikingly, does not target DNA, or structured RNA, targets other ADP-ribosyltransferases. Instead, modifies N6 position adenine GA dinucleotides within single-stranded RNAs arrest mRNA translation inhibition replication. work reveals new mechanism anti-viral previously unknown but broadly class ADP-ribosyltransferases mRNA.

Language: Английский

Citations

7
Beyond protein modification: the rise of non-canonical ADP-ribosylation DOI Creative Commons
M. Schuller, Ivan Ahel

Biochemical Journal, Journal Year: 2022, Volume and Issue: 479(4), P. 463 - 477

Published: Feb. 17, 2022

ADP-ribosylation has primarily been known as post-translational modification of proteins. As signalling strategy conserved in all domains life, it modulates substrate activity, localisation, stability or interactions, thereby regulating a variety cellular processes and microbial pathogenicity. Yet over the last years, there is increasing evidence non-canonical forms that are catalysed by certain members ADP-ribosyltransferase family go beyond traditional protein signalling. New macromolecular targets such nucleic acids new ADP-ribose derivatives have established, notably extending repertoire Based on physiological relevance so far, deserves its recognition next to which we therefore review following.

Language: Английский

Citations

27
Medicinal Chemistry Perspective on Targeting Mono-ADP-Ribosylating PARPs with Small Molecules DOI Creative Commons
Maria Giulia Nizi, Mirko M. Maksimainen, L. Lehtiö

et al.

Journal of Medicinal Chemistry, Journal Year: 2022, Volume and Issue: 65(11), P. 7532 - 7560

Published: May 24, 2022

Major advances have recently defined functions for human mono-ADP-ribosylating PARP enzymes (mono-ARTs), also opening up potential applications targeting them to treat diseases. Structural biology combined with medicinal chemistry has allowed the design of potent small molecule inhibitors which typically bind catalytic domain. Most these are at early stages, but some already a suitable profile be used as chemical tools. One compound PARP7 even progressed clinical trials. In this review, we collect mono-ARTs typical "H–Y−Φ" motif (Φ = hydrophobic residue) and focus on compounds that been reported active against one or restricted number enzymes. We discuss from point view include an analysis available crystal structures, allowing us craft pharmacophore model lays foundation obtaining new more specific inhibitors.

Language: Английский

Citations

25
Phages reconstitute NAD+to counter bacterial immunity DOI Creative Commons
Ilya А. Osterman,

Hadar Samra,

François Rousset

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 13, 2024

Abstract Bacteria defend against phage infection via a variety of antiphage defense systems. Many systems were recently shown to deplete cellular nicotinamide adenine dinucleotide (NAD + ) in response infection, by breaking NAD ADP-ribose (ADPR) and nicotinamide. It was demonstrated that depletion during deprives the from this essential molecule impedes replication. Here we show substantial fraction phages possess enzymatic pathways allowing reconstitution its degradation products infected cells. We describe pathway 1 (NARP1), two-step which one enzyme phosphorylates ADPR generate ADPR-pyrophosphate (ADPR-PP), second conjugates ADPR- PP . Phages encoding NARP1 can overcome diverse set systems, including Thoeris, DSR1, DSR2, SIR2-HerA, SEFIR, all as part their defensive mechanism. Phylogenetic analyses is primarily encoded on genomes, suggesting phage- specific function countering bacterial defenses. A pathway, NARP2, allows defenses building metabolites different than ADPR-PP. Our findings report unique immune evasion strategy where viruses rebuild molecules depleted thus overcoming host immunity.

Language: Английский

Citations

6
ADP-Ribosylation Post-Translational Modification: An Overview with a Focus on RNA Biology and New Pharmacological Perspectives DOI Creative Commons
Giuseppe Manco, Giuseppina Lacerra, Elena Porzio

et al.

Biomolecules, Journal Year: 2022, Volume and Issue: 12(3), P. 443 - 443

Published: March 13, 2022

Cellular functions are regulated through the gene expression program by transcription of new messenger RNAs (mRNAs), alternative RNA splicing, and protein synthesis. To this end, post-translational modifications (PTMs) proteins add another layer complexity, creating a continuously fine-tuned regulatory network. ADP-ribosylation (ADPr) is an ancient reversible modification cellular macromolecules, regulating multitude key functional processes as diverse DNA damage repair (DDR), transcriptional regulation, intracellular transport, immune stress responses, cell survival. Additionally, due to emerging role in pathological processes, ADP-ribosyltransferases (ARTs), enzymes involved ADPr, attracting growing interest drug targets. In review, overview human ARTs their related biological provided, mainly focusing on regulation ADP-ribosyltransferase Diphtheria toxin-like (ARTD)-dependent functions. Finally, order unravel novel relationships, we propose analysis inventory clusters, including ARTDs, which share conserved sequences at 3′ untranslated regions (UTRs).

Language: Английский

Citations

21