The plant immune system: From discovery to deployment

Cell, Journal Year: 2024, Volume and Issue: 187(9), P. 2095 - 2116

Published: April 1, 2024

Plant diseases cause famines, drive human migration, and present challenges to agricultural sustainability as pathogen ranges shift under climate change. breeders discovered Mendelian genetic loci conferring disease resistance specific isolates over 100 years ago. Subsequent breeding for underpins modern agriculture and, along with the emergence focus on model plants genetics genomics research, has provided rich resources molecular biological exploration last 50 years. These studies led identification of extracellular intracellular receptors that convert recognition microbe-encoded patterns or pathogen-delivered virulence effectors into defense activation. receptor systems, downstream responses, define plant immune systems have evolved since migration land ∼500 million Our current understanding provides platform development rational enhancement control many continue plague crop production.

Language: Английский

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Activation of the helper NRC4 immune receptor forms a hexameric resistosome

Cell, Journal Year: 2024, Volume and Issue: 187(18), P. 4877 - 4889.e15

Published: Aug. 1, 2024

Language: Английский

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A disease resistance protein triggers oligomerization of its NLR helper into a hexameric resistosome to mediate innate immunity

Science Advances, Journal Year: 2024, Volume and Issue: 10(45)

Published: Nov. 6, 2024

NRCs are essential helper NLR (nucleotide-binding domain and leucine-rich repeat) proteins that execute immune responses triggered by sensor NLRs. The resting state of NbNRC2 was recently shown to be a homodimer, but the sensor-activated remains unclear. Using cryo-EM, we determined structure NbNRC2, which forms hexameric inflammasome-like resistosome. Mutagenesis oligomerization interface abolished signaling, confirming functional significance Comparative structural analyses between homodimer homohexamer revealed substantial rearrangements, providing insights into activation mechanisms. Furthermore, comparisons hexamer previously reported CC-NLR pentameric assemblies features allowing an additional protomer integration. structure, assessed released AlphaFold 3 for predicting activated oligomers, revealing high-confidence modeling other amino-terminal α1 helices, region proven difficult resolve structurally. Overall, our work sheds light on mechanisms expands understanding diversity.

Language: Английский

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Engineering the plant intracellular immune receptor Sr50 to restore recognition of the AvrSr50 escape mutant

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

Published: Aug. 9, 2024

Abstract Sr50, an intracellular nucleotide-binding leucine-rich repeat receptor (NLR), confers resistance of wheat against stem rust caused by the fungal pathogen Puccinia graminis f. sp. tritici . The recognizes effector AvrSr50 through its C-terminal domain, initiating a localized cell death immune response. However, this immunity is compromised mutations in effector, as escape mutant QCMJC , which evades Sr50 detection. In study, we employed iterative computational structural analyses and site-directed mutagenesis for rational engineering to gain recognition Following initial hypothesis driven molecular docking, identified K711D single mutant, induces intermediate response without losing AvrSr50. Increasing gene expression with stronger promoter enabled elicit robust response, indicating weak can be complemented enhanced expression. Further refinements led creation five double mutants two triple dual greater intensities than mutant. All effective required substitution, that multiple solutions exist recognition, but path reach these may confined. Furthermore, substitution alters prediction AlphaFold 2, allowing it model complex structure match our final hypothesis. Collectively, study outlines framework NLR systems overcome provides datasets future models resurrection.

Language: Английский

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NLR‐mediated antiviral immunity in plants

Journal of Integrative Plant Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 7, 2025

ABSTRACT Plant viruses cause substantial agricultural devastation and economic losses worldwide. nucleotide‐binding domain leucine‐rich repeat receptors (NLRs) play a pivotal role in detecting viral infection activating robust immune responses. Recent advances, including the elucidation of interaction mechanisms between NLRs pathogen effectors, discovery helper NLRs, resolution ZAR1 resistosome structure, have significantly deepened our understanding NLR‐mediated responses, marking new era NLR research. In this scenario, significant progress has been made study antiviral immunity. This review comprehensively summarizes plant research over past decades, with focus on recognition activation regulation, downstream signaling, engineering NLRs.

Language: Английский

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Lessons from Deep Learning Structural Prediction of Multistate Multidomain Proteins—The Case Study of Coiled-Coil NOD-like Receptors

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(2), P. 500 - 500

Published: Jan. 9, 2025

We test here the prediction capabilities of new generation deep learning predictors in more challenging situation multistate multidomain proteins by using as a case study coiled-coil family Nucleotide-binding Oligomerization Domain-like (NOD-like) receptors from A. thaliana and few extra examples for reference. Results reveal truly remarkable ability these platforms to correctly predict 3D structure modules that fold well-established topologies. A lower performance is noticed modeling morphing regions proteins, such coiled coils. Predictors also display good sensitivity local sequence drifts upon solution overall modular configuration. In multivalued 1D mappings, marked tendency model most compact configuration must be retrained information filtering drive toward sparser ones. Bias order compactness seen at secondary level well. All all, AI when global templates are hand fruitful, but above challenges have taken into account. absence templates, piecewise approach with experimentally constrained reconstruction architecture might give realistic results.

Language: Английский

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A hierarchical immune receptor network in lettuce reveals contrasting patterns of evolution in sensor and helper NLRs

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

ABSTRACT Nucleotide-binding domain and leucine-rich repeat immune receptors (NLRs) are known for their rapid evolution, even at the intraspecific level, yet rates of evolution differ significantly across various NLR classes. Within NRC (NLR Required Cell Death) network, NLRs operate in complex sensor-helper configurations to confer immunity against a diverse array pathogens, particularly Asterids. While helper typically conserved evolve slowly, sensor tend more rapidly. However, functional connections between slow fast-evolving remain poorly understood, notably important crop species. We conducted comparative analysis 40 Solanales 29 Asterales genomes explore network expansion diversification within less-studied order. Our findings reveal that has expanded less compared Solanales. functionally validated minimal with 2 helpers 9 sensors common lettuce ( Lactuca sativa ). Through selection structural modeling subclades genus, we found varying evolutionary sensors. correlation dependency, reliant on phylogenetically experiencing limited pressure. results highlight lineage- function-specific offering insights into pressures shaping plant receptor networks.

Language: Английский

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Helper NLR immune protein NRC3 evolved to evade inhibition by a cyst nematode virulence effector

PLoS Genetics, Journal Year: 2025, Volume and Issue: 21(4), P. e1011653 - e1011653

Published: April 9, 2025

Parasites can counteract host immunity by suppressing nucleotide binding and leucine-rich repeat (NLR) proteins that function as immune receptors. We previously showed a cyst nematode virulence effector SPRYSEC15 (SS15) binds inhibits oligomerisation of helper NLR in the expanded NRC1/2/3 clade preventing intramolecular rearrangements required for NRC into an activated resistosome. Here we examined degree to which from multiple Solanaceae species are sensitive suppression SS15 tested hypotheses about adaptive evolution interface between inhibitor proteins. Whereas all orthologs NRC2 were inhibited SS15, some natural variants NRC1 NRC3 insensitive suppression. Ancestral sequence reconstruction combined with functional assays revealed transitioned ancestral suppressed form one over 19 million years ago. Our analyses evolutionary trajectory receptor against parasite inhibitor, identifying key transitions NLRs this inhibition. This work reveals distinct type gene-for-gene interaction or pathogen immunosuppressors receptors contrasts coevolution AVR effectors

Language: Английский

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Diversification of the “EDVID” packing motif underpins structural and functional variation in plant NLR coiled-coil domains

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: June 3, 2025

Summary Nucleotide-binding leucine-rich repeat receptors (NLRs) are critical in plant immunity and display remarkable allelic diversity. Coiled-coiled NLRs (CC-NLRs) the most widespread group of these found across flowering non-flowering plants. Here we investigate sequence conservation functional variation conserved EDVID motif α3-helix cell death inducing CC domain NLRs. We analyse our findings context published protein structures structure prediction. find that can serve as a predictor canonical CC-NLR function oligomeric assembly. also is accompanied by preceding acidic residues certain CC-NLRs with homology to Arabidopsis RPP8. The appearance this so-called preEDVID phylogeny plants its contribution underpins structural diversity motif. further show exist have lost suggesting subgroup, previously referred G10 -NLRs, functions different manner from mechanism. located helper NLR NRG1.1 linked activity.

Language: Английский

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Can AI modelling of protein structures distinguish between sensor and helper NLR immune receptors?

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

Published: Nov. 26, 2024

ABSTRACT NLR immune receptors can be functionally organized in genetically linked sensor-helper pairs. However, methods to categorize paired NLRs remain limited, primarily relying on the presence of non-canonical domains some sensor NLRs. Here, we propose that AI system AlphaFold 3 classify proteins into or helper categories based predicted structural characteristics. Helper showed higher confidence scores than sensors when modelled oligomeric configurations. Furthermore, funnel-shaped structures—essential for activating responses—were reliably helpers but not sensors. Applying this method uncharacterized pairs from rice, found differentiate between putative and even both lack domain annotations. These findings suggest offers a new approach enhances our understanding functional configurations plant systems, absence

Language: Английский

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