Identification and receptor mechanism of TIR-catalyzed small molecules in plant immunity

Science, Journal Year: 2022, Volume and Issue: 377(6605)

Published: July 7, 2022

Plant nucleotide-binding leucine-rich repeat-containing (NLR) receptors with an N-terminal Toll/interleukin-1 receptor (TIR) domain sense pathogen effectors to enable TIR-encoded nicotinamide adenine dinucleotide hydrolase (NADase) activity for immune signaling. TIR-NLR signaling requires the helper NLRs N requirement gene 1 (NRG1), Activated Disease Resistance (ADR1), and Enhanced Susceptibility (EDS1), which forms a heterodimer each of its paralogs Phytoalexin Deficient 4 (PAD4) Senescence-Associated Gene 101 (SAG101). Here, we show that TIR-containing proteins catalyze production 2'-(5''-phosphoribosyl)-5'-adenosine monophosphate (pRib-AMP) diphosphate (pRib-ADP) in vitro planta. Biochemical structural data demonstrate EDS1-PAD4 is complex pRib-AMP pRib-ADP, allosterically promote interaction ADR1-L1 but not NRG1A. Our study identifies TIR-catalyzed pRib-ADP as missing link TIR through likely second messengers plant immunity.

Language: Английский

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TIR-catalyzed ADP-ribosylation reactions produce signaling molecules for plant immunity

Science, Journal Year: 2022, Volume and Issue: 377(6605)

Published: July 7, 2022

Plant pathogen-activated immune signaling by nucleotide-binding leucine-rich repeat (NLR) receptors with an N-terminal Toll/interleukin-1 receptor (TIR) domain converges on Enhanced Disease Susceptibility 1 (EDS1) and its direct partners, Phytoalexin Deficient 4 (PAD4) or Senescence-Associated Gene 101 (SAG101). TIR-encoded nicotinamide adenine dinucleotide hydrolase (NADase) produces molecules to promote exclusive EDS1-PAD4 EDS1-SAG101 interactions helper NLR subclasses. In this work, we show that TIR-containing proteins catalyze adenosine diphosphate (ADP)-ribosylation of triphosphate (ATP) ADP ribose (ADPR) through ADPR polymerase-like NADase activity, forming ADP-ribosylated ATP (ADPr-ATP) ADPr-ADPR (di-ADPR), respectively. Specific binding ADPr-ATP di-ADPR allosterically promotes interaction N requirement gene 1A (NRG1A) in vitro planta. Our data reveal enzymatic activity TIRs enables specific activation the EDS1-SAG101-NRG1 immunity branch.

Language: Английский

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Shared TIR enzymatic functions regulate cell death and immunity across the tree of life

Science, Journal Year: 2022, Volume and Issue: 377(6605)

Published: July 7, 2022

In the 20th century, researchers studying animal and plant signaling pathways discovered a protein domain that is shared across diverse innate immune systems: Toll/interleukin-1/resistance gene (TIR) domain. The TIR found in several architectures was defined as an adaptor mediates protein-protein interactions immunity developmental pathways. However, studies of nerve degeneration animals-and subsequent breakthroughs plant, bacterial, archaeal systems-revealed domains possess enzymatic activities. We provide synthesis functions role various related products evolutionarily systems. These may ultimately guide interventions would span tree life, from treating human neurodegenerative disorders bacterial infections to preventing diseases.

Language: Английский

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Oligomerization of a plant helper NLR requires cell-surface and intracellular immune receptor activation

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(11)

Published: March 6, 2023

Plant disease resistance involves both detection of microbial molecular patterns by cell-surface pattern recognition receptors and pathogen effectors intracellular NLR immune receptors. NLRs are classified as sensor NLRs, involved in effector detection, or helper required for signaling. TIR-domain-containing (TNLs) require NRG1 ADR1 resistance, activation defense requires the lipase-domain proteins EDS1, SAG101, PAD4. Previously, we found that associates with EDS1 SAG101 a TNL activation-dependent manner [X. Sun et al. , Nat. Commun. 12 3335 (2021)]. We report here how itself during TNL-initiated immunity. Full immunity coactivation mutual potentiation receptor-initiated signaling [B. P. M. Ngou, H.-K. Ahn, Ding, J. D. G. Jones, Nature 592 110–115 (2021), Yuan 105–109 find while TNLs is sufficient to promote NRG1–EDS1–SAG101 interaction, formation an oligomeric resistosome additional defense. These data suggest vivo part mechanism links receptor pathways.

Language: Английский

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Plant NLR immunity activation and execution: a biochemical perspective

Open Biology, Journal Year: 2024, Volume and Issue: 14(1)

Published: Jan. 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.

Language: Английский

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Balanced plant helper NLR activation by a modified host protein complex

Nature, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 12, 2025

Language: Английский

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Structure, biochemical function, and signaling mechanism of plant NLRs

Molecular Plant, Journal Year: 2022, Volume and Issue: 16(1), P. 75 - 95

Published: Nov. 22, 2022

To counter pathogen invasion, plants have evolved a large number of immune receptors, including membrane-resident pattern recognition receptors (PRRs) and intracellular nucleotide-binding leucine-rich repeat (NLRs). Our knowledge about PRR NLR signaling mechanisms has expanded significantly over the past few years. Plant NLRs form multi-protein complexes called resistosomes in response to effectors, mediated by converges on Ca2+-permeable channels. channels important for also been identified. These findings highlight crucial role Ca2+ triggering plant signaling. In this review, we first discuss structural biochemical non-canonical then summarize our immune-related their roles We potential intricate interaction between

Language: Английский

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TIR-domain enzymatic activities at the heart of plant immunity

Current Opinion in Plant Biology, Journal Year: 2023, Volume and Issue: 74, P. 102373 - 102373

Published: May 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.

Language: Английский

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New Biochemical Principles for NLR Immunity in Plants

Molecular Plant-Microbe Interactions, Journal Year: 2023, Volume and Issue: 36(8), P. 468 - 475

Published: Aug. 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 .

Language: Английский

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Defense signaling pathways in resistance to plant viruses: Crosstalk and finger pointing

Advances in virus research, Journal Year: 2024, Volume and Issue: unknown, P. 77 - 212

Published: Jan. 1, 2024

Language: Английский

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