Pathogen protein modularity enables elaborate mimicry of a host phosphatase

Li, Hui; Wang, Jinlong; Kuan, Tung; Tang, Bozeng; Liu, Feng; Wang, Jiuyu; Cheng, Zhi; Sklenář, Jan; Derbyshire, Paul; Hulin, Michelle T.; Li, Yufei; Zhai, Yi; Hou, Yingnan; Menke, Frank L. H.; Wang, Yanli; Ma, Wenbo

doi:10.1016/j.cell.2023.05.049

Cited by 24 publications

(4 citation statements)

References 45 publications

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“…These effectors produced by Phytophthora possess a functional module formed by a specific (L)WY-LWY combination, which efficiently recruits the host serine-threonine protein phosphatase 2A (PP2A) core enzyme ( 49 ). By hijacking the host PP2A core enzyme through this (L)WY-LWY module, the effectors form functional holoenzymes that enable the manipulation of host cellular processes, contributing to the pathogen’s virulence ( 49 ). Thus, both pathogens and host plants use strategies to alter the preference of enzymes to benefit themselves.…”

Section: Discussionmentioning

confidence: 99%

A plant mechanism of hijacking pathogen virulence factors to trigger innate immunity

Xiao,

Sun,

et al. 2024

Science

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Polygalacturonase-inhibiting proteins (PGIPs) interact with pathogen-derived polygalacturonases to inhibit their virulence-associated plant cell wall–degrading activity but stimulate immunity-inducing oligogalacturonide production. Here we show that interaction between Phaseolus vulgaris PGIP2 (PvPGIP2) and Fusarium phyllophilum polygalacturonase (FpPG) enhances substrate binding, resulting in inhibition of the enzyme activity of FpPG. This interaction promotes FpPG-catalyzed production of long-chain immunoactive oligogalacturonides, while diminishing immunosuppressive short oligogalacturonides. PvPGIP2 binding creates a substrate binding site on PvPGIP2-FpPG, forming a new polygalacturonase with boosted substrate binding activity and altered substrate preference. Structure-based engineering converts a putative PGIP that initially lacks FpPG-binding activity into an effective FpPG-interacting protein. These findings unveil a mechanism for plants to transform pathogen virulence activity into a defense trigger and provide proof of principle for engineering PGIPs with broader specificity.

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Section: Discussionmentioning

confidence: 99%

A plant mechanism of hijacking pathogen virulence factors to trigger innate immunity

Xiao,

Sun,

et al. 2024

Science

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“…He et al ., 2019; Hou et al ., 2019; Zhang et al ., 2019). Recently, a functional L(WY)‐LWY module was identified in 12 effectors from two Phytophthora species that recruit and hijack a Serine/Threonine protein phosphatase 2A (PP2A) core enzyme, with polymorphisms in the C‐terminal LWY module altering the specificity for targeted host phosphatases (Hui et al ., 2023). Here, we observed that AvrSr27 consists of two structurally similar domains, indicating that some Pgt effectors, like Phytophthora and bacterial effectors, likely utilise repeated core structural modules.…”

Section: Discussionmentioning

confidence: 99%

AvrSr27 is a zinc‐bound effector with a modular structure important for immune recognition

Outram,

Chen,

Broderick

et al. 2024

New Phytologist

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Summary Effector proteins are central to the success of plant pathogens, while immunity in host plants is driven by receptor‐mediated recognition of these effectors. Understanding the molecular details of effector–receptor interactions is key for the engineering of novel immune receptors. Here, we experimentally determined the crystal structure of the Puccinia graminis f. sp. tritici (Pgt) effector AvrSr27, which was not accurately predicted using AlphaFold2. We characterised the role of the conserved cysteine residues in AvrSr27 using in vitro biochemical assays and examined Sr27‐mediated recognition using transient expression in Nicotiana spp. and wheat protoplasts. The AvrSr27 structure contains a novel β‐strand rich modular fold consisting of two structurally similar domains that bind to Zn2+ ions. The N‐terminal domain of AvrSr27 is sufficient for interaction with Sr27 and triggering cell death. We identified two Pgt proteins structurally related to AvrSr27 but with low sequence identity that can also associate with Sr27, albeit more weakly. Though only the full‐length proteins, trigger Sr27‐dependent cell death in transient expression systems. Collectively, our findings have important implications for utilising protein prediction platforms for effector proteins, and those embarking on bespoke engineering of immunity receptors as solutions to plant disease.

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“…Protein purification, immunoprecipitation, sample preparation, liquid chromatography followed by tandem mass spectrometry (LC-MS/MS), and data analysis were previously described in full detail (64). Briefly proteins identified in immunoaffinity-enriched samples were measured with data dependent method on high resolution LC-MS systems, Orbitrap Fusion (Thermo Ltd).…”

Section: Mass Spectrometry and Data Processingmentioning

confidence: 99%

The blast effector Pwl2 is a virulence factor that modifies the cellular localisation of host protein HIPP43 to suppress immunity

Were,

Yan,

Foster

et al. 2024

Preprint

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The rice blast fungusMagnaporthe oryzaesecretes a battery of effector proteins during host infection to suppress plant immunity and promote disease. Among these effectors, the MAX effector-Pwl2 was first identified as a host specificity determinant for infection of weeping lovegrass (Eragrostis curvula). However, its biological activity has remained unknown. Here we show that thePWL2gene is ubiquitous in all host-limited forms ofM. oryzaeand has undergone substantial copy number expansion indicating that it is a core effector of the blast fungus. We used CRISPR/Cas9-mediated gene editing to delete all three copies ofPWL2and generate apwl2null mutant inM. oryzaestrain Guy11. This resulted in gain-of-virulence towards weeping lovegrass, but a reduction in the severity of disease symptoms on rice. To further investigate the virulence mechanism of Pwl2, we showed that transgenic rice and barley lines constitutively expressingPWL2display suppression of reactive oxygen species generation and increased susceptibility to infection byM. oryzae. Also, we identify the barley and rice heavy metal-binding isoprenylated protein HIPP43 as a target of the Pwl2 effector. Transgenic lines overexpressing HIPP43 exhibit attenuated defense responses and increased susceptibility to blast infection, consistent with the hypothesis that Pwl2 binds HIPP43 to modulate immunity. This binding is coupled to changes in cellular localisation of these proteins. Taken together, our results provide evidence that Pwl2 is a virulence factor inM. oryzaethat acts by suppressing host immunity through binding and re-localising HIPP43.

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Pathogen protein modularity enables elaborate mimicry of a host phosphatase

Cited by 24 publications

References 45 publications

A plant mechanism of hijacking pathogen virulence factors to trigger innate immunity

A plant mechanism of hijacking pathogen virulence factors to trigger innate immunity

AvrSr27 is a zinc‐bound effector with a modular structure important for immune recognition

The blast effector Pwl2 is a virulence factor that modifies the cellular localisation of host protein HIPP43 to suppress immunity

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