NLR signaling in plants: from resistosomes to second messengers

Trends in Biochemical Sciences, Год журнала: 2023, Номер 48(9), С. 776 - 787

Опубликована: Июнь 30, 2023

Pathogen effector-induced assembly of resistosomes has been established as an important event for nucleotide binding and leucine-rich repeat-containing receptor (NLR) signaling in plants.The pentameric coiled-coil domain-containing NLR (CNL) act Ca2+-permeable channels, whereas the tetrameric Toll-interleukin 1-like (TIR) (TNL) are NADase holoenzymes.TNL catalyze production nucleotide-derived second messengers to activate downstream helper NLRs activated disease resistance 1 (ADR1) N requirement gene (NRG1) CNL class. Thus, CNLs TNLs converge on Ca2+ signals trigger plant immunity.NLR cross-talks with pattern-triggered immunity (PTI) pathways.NLR pathways plants negatively regulated by both hosts pathogens. Nucleotide receptors (NLRs) have a critical role through direct or indirect recognition pathogen effectors. Recent studies demonstrated that such induces formation large protein complexes called mediate immune signaling. Some influx acting others function active NADases messengers. 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Язык: Английский

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Conservation and similarity of bacterial and eukaryotic innate immunity

Nature Reviews Microbiology, Год журнала: 2024, Номер 22(7), С. 420 - 434

Опубликована: Фев. 28, 2024

Язык: Английский

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Plant NLR immunity activation and execution: a biochemical perspective

Open Biology, Год журнала: 2024, Номер 14(1)

Опубликована: Янв. 1, 2024

Plants deploy cell-surface and intracellular receptors to detect pathogen attack trigger innate immune responses. Inside host cells, families of nucleotide-binding/leucine-rich repeat (NLR) proteins serve as sensors or downstream mediators defence outputs cell death, which prevent disease. Established genetic underpinnings NLR-mediated immunity revealed various strategies plants adopt combat rapidly evolving microbial pathogens. The molecular mechanisms NLR activation signal transmission components controlling execution were less clear. Here, we review recent protein structural biochemical insights plant sensor signalling functions. When put together, the data show how different families, whether transducers, converge on nucleotide-based second messengers cellular calcium confer immunity. Although pathogen-activated NLRs in engage plant-specific machineries promote defence, comparisons with mammalian receptor counterparts highlight some shared working principles for across kingdoms.

Язык: Английский

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Substrate-induced condensation activates plant TIR domain proteins

Nature, Год журнала: 2024, Номер 627(8005), С. 847 - 853

Опубликована: Март 13, 2024

Abstract Plant nucleotide-binding leucine-rich repeat (NLR) immune receptors with an N-terminal Toll/interleukin-1 receptor (TIR) domain mediate recognition of strain-specific pathogen effectors, typically via their C-terminal ligand-sensing domains 1 . Effector binding enables TIR-encoded enzymatic activities that are required for TIR–NLR (TNL)-mediated immunity 2,3 Many truncated TNL proteins lack effector-sensing but retain similar and 4,5 The mechanism underlying the activation these TIR remain unclear. Here we show substrates NAD + ATP induces phase separation in vitro. A condensation occurs a protein expressed its native promoter response to inoculation planta. formation condensates is mediated by conserved self-association interfaces predicted intrinsically disordered loop region TIRs. Mutations disrupt impair cell death activity proteins. Our data reveal as provide insight into substrate-induced autonomous signalling confer plant immunity.

Язык: Английский

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TIR signaling activates caspase-like immunity in bacteria

Science, Год журнала: 2025, Номер 387(6733), С. 510 - 516

Опубликована: Янв. 30, 2025

Caspase family proteases and Toll/interleukin-1 receptor (TIR)-domain proteins have central roles in innate immunity regulated cell death humans. We describe a bacterial immune system comprising both caspase-like protease TIR-domain protein. found that the TIR protein, once it recognizes phage invasion, produces previously unknown signaling molecule adenosine 5′-diphosphate-cyclo[N7:1′′]-ribose (N7-cADPR). This specifically activates protease, which then indiscriminately degrades cellular to halt replication. The TIR-caspase defense system, we denote as type IV Thoeris, is abundant bacteria efficiently protects against propagation. Our study highlights diversity of TIR-produced molecules demonstrates by caspase an ancient mechanism immunity.

Язык: Английский

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Structural insights into mechanisms of Argonaute protein-associated NADase activation in bacterial immunity

Cell Research, Год журнала: 2023, Номер 33(9), С. 699 - 711

Опубликована: Июнь 13, 2023

Nicotinamide adenine dinucleotide (NAD+) is a central metabolite in cellular processes. Depletion of NAD+ has been demonstrated to be prevalent theme both prokaryotic and eukaryotic immune responses. Short Argonaute proteins (Agos) are associated with NADase domain-containing (TIR-APAZ or SIR2-APAZ) encoded the same operon. They confer immunity against mobile genetic elements, such as bacteriophages plasmids, by inducing depletion upon recognition target nucleic acids. However, molecular mechanisms underlying activation NADase/Ago systems remain unknown. Here, we report multiple cryo-EM structures complexes from two distinct (TIR-APAZ/Ago SIR2-APAZ/Ago). Target DNA binding triggers tetramerization TIR-APAZ/Ago complex cooperative self-assembly mechanism, while heterodimeric SIR2-APAZ/Ago does not assemble into higher-order oligomers binding. activities these unleashed via similar closed-to-open transition catalytic pocket, albeit different mechanisms. Furthermore, functionally conserved sensor loop employed inspect guide RNA-target base pairing facilitate conformational rearrangement Ago required for systems. Overall, our study reveals mechanistic diversity similarity protein-associated response.

Язык: Английский

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Calcium homeostasis and signaling in plant immunity

Current Opinion in Plant Biology, Год журнала: 2023, Номер 77, С. 102485 - 102485

Опубликована: Дек. 2, 2023

Calcium (Ca2+) signaling consists of three steps: (1) initiation a change in cellular Ca2+ concentration response to stimulus, (2) recognition the through direct binding by its sensors, (3) transduction signal elicit downstream responses. Recent studies have uncovered central role for both layers immune responses initiated plasma membrane (PM) and intracellular receptors, respectively. These advances our understanding are attributed several lines research, including invention genetically-encoded reporters recording signals, identification channels their gating mechanisms, functional analysis proteins (Ca2+ sensors). This review analyzes recent literature that illustrates importance homeostasis plant innate immunity, featuring intricate Ca2+dependent positive negative regulations.

Язык: Английский

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Pangenomic analysis reveals plant NAD ⁺ manipulation as an important virulence activity of bacterial pathogen effectors

Proceedings of the National Academy of Sciences, Год журнала: 2023, Номер 120(7)

Опубликована: Фев. 8, 2023

Nicotinamide adenine dinucleotide (NAD + ) has emerged as a key component in prokaryotic and eukaryotic immune systems. The recent discovery that Toll/interleukin-1 receptor (TIR) proteins function NAD hydrolases (NADase) links -derived small molecules with signaling. We investigated pathogen manipulation of host metabolism virulence strategy. Using the pangenome model bacterial Pseudomonas syringae , we conducted structure-based similarity search from 35,000 orthogroups for type III effectors (T3Es) potential NADase activity. Thirteen T3Es, including five newly identified candidates, were possess domain(s) characteristic seven -hydrolyzing enzyme families. Most strains depend on secretion system to cause disease, encode at least one -manipulating T3E, many have several. experimentally confirmed III-dependent novel named HopBY, which shows structural both TIR adenosine diphosphate ribose (ADPR) cyclase. Homologs HopBY predicted be VI diverse species, indicating recruitment this activity by microbial secreted during various interspecies interactions. efficiently hydrolyzes specifically produces 2′cADPR, can also produced receptors plants other bacteria. Intriguingly, effector promoted virulence, 2′cADPR may not signaling molecule directly initiates immunity. This study highlights host-pathogen battleground centered around provides insight into involved plant

Язык: Английский

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TIR-domain enzymatic activities at the heart of plant immunity

Current Opinion in Plant Biology, Год журнала: 2023, Номер 74, С. 102373 - 102373

Опубликована: Май 5, 2023

Toll/interleukin-1/resistance (TIR) domain proteins contribute to innate immunity in all cellular kingdoms. TIR modules are activated by self-association and plants, mammals bacteria, some TIRs have enzymatic functions that crucial for disease resistance and/or cell death. Many plant TIR-only pathogen effector-activated TIR-domain NLR receptors NAD+ hydrolysing enzymes. Biochemical, structural functional studies established both TIR-protein types, certain bacterial TIRs, NADase activity generates bioactive signalling intermediates which promote resistance. A set of TIR-catalysed nucleotide isomers was discovered bind activate EDS1 complexes, promoting their interactions with co-functioning helper NLRs. Analysis enzymes across kingdoms fills an important gap understanding how disturbance induces TIR-regulated immune responses.

Язык: Английский

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New Biochemical Principles for NLR Immunity in Plants

Molecular Plant-Microbe Interactions, Год журнала: 2023, Номер 36(8), С. 468 - 475

Опубликована: Авг. 1, 2023

While working for the United States Department of Agriculture on North Dakota Agricultural College campus in Fargo, Dakota, 1940s and 1950s, Harold H. Flor formulated genetic principles coevolving plant host-pathogen interactions that govern disease resistance or susceptibility. His ‘gene-for-gene’ legacy runs deep modern pathology continues to inform molecular models immune recognition signaling. In this review, we discuss recent biochemical insights immunity conferred by nucleotide-binding domain/leucine-rich-repeat (NLR) receptors, which are major gene-for-gene determinants nature cultivated crops. Structural analyses pathogen-activated NLR oligomers (resistosomes) reveal how different subtypes converge various ways calcium (Ca 2+ ) signaling promote pathogen host cell death. Especially striking is identification nucleotide-based signals generated enzymatically toll-interleukin 1 receptor (TIR) domain NLRs. These small molecules part an emerging family TIR-produced cyclic noncyclic nucleotide steer cell-death responses bacteria, mammals, plants. A combined genetic, molecular, understanding activation provides exciting new opportunities combatting diseases [Formula: see text] Copyright © 2023 The Author(s). This open access article distributed under CC BY-NC-ND 4.0 International license .

Язык: Английский

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