Structural Insights Into the Role of RxLR Effectors in the Arms Race Between Oomycetes and Plants

ABSTRACT

Oomycetes threaten food security, with RxLR effectors playing a key role in their pathogenesis by modulating host–pathogen signalling and suppressing plant immune responses. A growing body of research has elucidated how RxLR effectors manipulate plant immune responses to achieve successful infection. Despite progress, the correlation between the structure and function of oomycete RxLR effectors is not fully understood. This review consolidates existing knowledge on the structure–function relationships of resolved effectors, offering a framework to understand their mechanisms during host–pathogen interactions and proposing insights for engineering resistant crop varieties.

Oomycete RxLR effectors promote infection and host colonisation by modulating autophagy, host enzymatic activity, RNA transcription, and plant immunity. Decoding their structure–function relationships facilitates innovative oomycete disease control and disease‐resistant crop breeding.

1. Introduction

Ensuring food security is increasingly challenging due to climate change and population growth. Crop yields are threatened by pathogens like fungi, bacteria, viruses, nematodes and oomycetes (Wang et al. 2022). Oomycetes are eukaryotic organisms that belong to the Straminipila clade, which also includes diatoms and brown algae (Chen et al. 2023). Oomycetes can be categorised into three types: necrotrophs, biotrophs and hemibiotrophs, with hemibiotrophs initially acting like biotrophs during the early stages of infection, where they derive nutrients from living host cells. At the later stage (i.e., necrotrophic phase), hemibiotrophs kill host cells to feed on the cellular contents (Liao et al. 2022). Hemibiotrophs pose significant challenges to crop production due to their capability of infecting a diverse array of crops. For instance, Phytophthora cactorum, a hemibiotrophic oomycete pathogen, infects more than 200 plant species across 54 families, including Fragaria × ananassa (Chen et al. 2022; Deutschmann 1954). Another hemibiotrophic oomycete, Phytophthora infestans , is primarily responsible for potato late blight, but can also cause diseases in other solanaceous plants (Gao et al. 2020). Additionally, Phytophthora capsici affects peppers and cucurbits, and Phytophthora sojae is known to infect soybeans (Kamoun et al. 2015; McCoy et al. 2023; Tyler 2007; Vogel et al. 2022).

Plants combat oomycete infections with a two‐layered innate immune system. The first layer of defence is activated when extracellular receptors detect pathogen‐associated molecular patterns (PAMPs), initiating PAMP‐triggered immunity (PTI) (Bigeard et al. 2015; Pruitt et al. 2021). The second layer, effector‐triggered immunity (ETI), occurs when intracellular receptors detect oomycete effectors, leading to a stronger response than PTI (Remick et al. 2023). These immune responses converge to modify the transcription of defence genes, enabling plants to fight the pathogen (Yuan, Ngou, et al. 2021; Ngou et al. 2021; Yuan, Jiang, et al. 2021).

Cytoplasmic effectors of oomycetes are crucial for infecting and damaging plant hosts by suppressing immune responses and disrupting host cell functions. These effectors are key in oomycete pathogenesis, making them potential targets for developing disease resistance. Oomycete cytoplasmic effectors include RxLR effectors, characterised by a conserved N‐terminal Arg‐X‐Leu‐Arg (RXLR, where X denotes any amino acid) motif, and Crinkling and Necrosis (CRN) effectors, which harbour another conserved N‐terminal LXLFLAK motif (Wang, Wang, et al. 2023; Oh et al. 2024). Recent studies have revealed the structures of several RXLR effectors, shedding light on their role in manipulating plant immune responses and recognition by intracellular receptors (Table 1, Figure 1). This review updates our understanding of effector–plant receptor interactions, which are essential for designing resistance proteins in crops to combat these pathogens.

TABLE 1.

Structural information of oomycete RXLR effectors.

Effector	Target protein	Target protein type	PDB code	References
ATR13	RPP13	CC‐NB‐LRR protein	2LAI	Leonelli et al. (2011)
ATR1	RPP1	TIR‐NB‐LRR protein	7CRB, 7CRC, 3RMR	Chou et al. (2011) and Ma et al. (2020)
Avr3a	CMPG1	E3 ligase	2NAR	Wawra et al. (2017)
	DRP2	Dynamin‐related protein 2
PexRD2	MAPKKKs	MAPKK kinases	3ZRG	Boutemy et al. (2011)
AVR3a11	—	—	3ZR8	Boutemy et al. (2011)
PSR2	PP2A	Serine/threonine protein phosphatese 2A	5GNC, 7XVK	He et al. (2019) and Li et al. (2023)
PITG_15142	PP2A	Serine/threonine protein phosphatese 2A	7XVI	Li et al. (2023)
PexRD54	ATG8	Autophagy related protein 8	5L7S, 5L83	Maqbool et al. (2016)
PcRxLR12	—	—	5ZC3	Zhao et al. (2018)
SFI3	StUBK	U‐box kinase protein	6GU1	He et al. (2019)
PsAvh240	GmAP1	Aspartic protease	6J8L	Guo et al. (2019)
AVRvnt1	GLYK	Glycerate 3 kinase	7XP9, 7XPC	Unpublished
Pi03414	PP1c	Phosphatase 1 catalytic	8PQ7	Bentham et al. (2023)
PsAvr1d	GmPUB13	E3 ligase	7C96	Lin et al. (2021)

FIGURE 1.

Subcellular localisation of oomycete effectors and their plant targets. The plant proteins targeted by the effectors, capable of enhancing the immune response, are represented in light blue, whereas the targets whose manipulation increases susceptibility to the pathogen are illustrated in green. Arrows indicate the positive influence of each effector on its respective plant‐target activity, whereas blocked lines denote a negative effect. ER, endoplasmic reticulum; Golgi, Golgi apparatus; IE, intracellular effector; AE, apoplastic effector.

2. Oomycete Effectors Regulate Host Cell Autophagy

RxLR effectors of oomycetes typically possess a conserved RXLR motif along with a WY motif; in some cases, an additional LWY motif is also present, followed by a flexible C‐termini region (Figure 2). The RXLR motif mediates effector entry into host cells, although its molecular mechanism requires further elucidation. Despite low overall sequence conservation among RXLR effectors, their structural stability is preserved by the hydrophobic cores formed around conserved tryptophan: (W) and tyrosine (Y) residues in the WY and LWY motifs (Figure 2, Figure S1). Recent studies have shown that RXLR effectors enhance host susceptibility by targeting autophagy‐related proteins (ATGs), which are essential for autophagosome biogenesis. This interference disrupts autophagy, a critical cellular process responsible for recycling and degrading damaged components in plant cells. For example, the RXLR effector PpAvh195 from the hemibiotrophic Phytophthora parasitica interacts with ATG8s in Arabidopsis thaliana to inhibit autophagy, causing lysosome‐like structures to accumulate without fusing to vacuoles (Figure S2A) (Lenz et al. 2011; Testi et al. 2024). Similarly, the PexRD54 from the hemibiotrophic P. infestans binds to GTPase Rab8a, disrupting vesicle transport critical for plant resistance (Figure S2B) (Pandey et al. 2021). PexRD54 also diverts Rab8a from defence‐related autophagosomes to those involved in carbon starvation and competes with StJoka2 for binding to StATG8CL, increasing potato susceptibility (Figure S2B) (Dagdas et al. 2016; Pandey et al. 2021; Dagdas et al. 2018). Structural analysis of PexRD54 shows it contains five tandem WY motifs and a C‐termini AIM motif, with each WY motif contributing to a hydrophobic core (Figure S2C) (Maqbool et al. 2016). Homology structural alignment has demonstrated that the WY motifs of PexRD54 share structural similarities with AVR3a and AVR3a11, and the hydrophobic cores within these motifs are relatively conserved (Maqbool et al. 2016). Hydrophobic cores are crucial for stabilising the three‐dimensional structures of AVR3a and AVR3a11 (Pace et al. 2011; Zhang et al. 2018), and likely play a similar role in PexRD54 (Maqbool et al. 2016). Structural analysis of PexRD54 revealed it binds to ATG8CL through hydrophobic interactions and salt bridges within a narrow channel (Figure S2D) (Maqbool et al. 2016). The side chains of W378, I380 and V381 in PexRD54 interact with I22, Y26 and V64 in ATG8CL, while D377 and E379 form salt bridges with K47 and R68 in ATG8CL (Figure S2D). The residues W378 and V381 are critical for binding to StATG8CL, underscoring the importance of the C‐termini AIM motif in inhibiting ATG8CL function (Figure S2D) (Maqbool et al. 2016).

FIGURE 2.

Structure diagram of distinct regions in RXLR effectors. The structural alignment of Pi03414, Avr3a11, Avr3a and PsAvr1d is shown in yellow, green, purple, and grey, respectively. A dashed line of different colours indicated an unknown structure in RXLR effector.

3. The Oomycete Effectors Regulate the RNA Transcription Process in Plants

Oomycetes infect plants by using effectors that target host transcriptional regulators (TRs), transcription factors (TFs) and RNA‐mediated silencing (RNAi) to suppress defence genes and enhance susceptibility genes. These effectors can also impact plant growth and development. For example, the hemibiotrophic oomycete Hyaloperonospora arabidopsidis, which causes downy mildew, secretes the effector HaRxL106 to target the A. thaliana protein AtRCD1, thereby suppressing the salicylic acid (SA) immune pathway and altering plant growth (Figure S3A) (Wirthmueller et al. 2018). Another H. arabidopsidis effector, HaRxL21, manipulates the TOPLESS protein, a key regulator of A. thaliana development, to suppress defence‐related genes (Figure S3A) (Harvey et al. 2020). Other effectors targeting TRs uninvolved in plant growth primarily modulate plant immune responses. For example, the effector PiSFI3 from P. infestans interacts with the potato U‐box kinase StUBK, consequently suppressing the transcription of early defence genes StWRKY7 and StACRE31 (Figure S3A) (He et al. 2019). Structural investigations into PiSFI3 have shown it forms a homodimer with extended α‐helices in each monomer aligning antiparallelly, featuring a conserved WY motif (He et al. 2019). Mutations at residues L86D, L100D and L103D disrupt homodimerisation, affecting localisation and virulence, highlighting the role of WY motifs in effector stability and function (He et al. 2019).

Some oomycete effectors target host transcription factors to suppress defences and increase susceptibility. For example, the P. infestans effector AVR2 induces the brassinosteroid (BR) signalling TF, StCHL1, in potatoes, enhancing susceptibility by promoting the expression of BR marker genes (Figure S3B) (Turnbull et al. 2017). The H. arabidopsidis effector HaRxLL470 interacts with the light‐responsive transcription factor AtHY5 in A. thaliana , obstructing its binding with downstream gene promoters and thereby diminishing the transcription of defence‐related genes (Figure S3B) (Chen et al. 2021). In A. thaliana , HaRxL45 targets AtTCP14, suppressing SA‐mediated immune responses and activating the jasmonic acid (JA) pathway, increasing susceptibility (Figure S3B) (Kieffer et al. 2011; Resentini et al. 2015; Zhang et al. 2019).

Oomycete effectors also disrupt the RNAi pathway, crucial for regulating plant defence‐related genes and balancing growth and immunity. For instance, the P. sojae effector PSR2 (PsPSR2) interacts with double‐stranded RNA binding protein 4 (AtDRB4) in the plant cytoplasm, inhibiting the host's RNAi process (Figure S3C) (Hou et al. 2019). Crystal structure analysis has revealed that PsPSR2 has seven tandem repeat units: a WY motif with three α‐helices and a hydrophobic core and six LWY motifs, each with five α‐helices and two hydrophobic cores, with stability between adjacent motifs achieved through interactions between adjacent motifs (He et al. 2019). The WY1, LWY2, and LWY6 motifs are essential for RNA silencing suppression, suggesting that distinct regions of the effector may serve specialised functions (He et al. 2019). Despite structural similarities, the diverse functions of (L)WY motifs remain to be fully understood.

4. Oomycete Effectors Affect the Enzymatic Catalysis of the Host

Oomycetes modulate host physiological and immune responses by secreting effectors that manipulate or mimic host enzyme functions, influencing disease resistance. For example, P. capsici effectors PcAVR3a12 and PcRXLR25 manipulate key enzymes in plant immune responses. PcAVR3a12 interacts with the endoplasmic reticulum‐localised immune protein, FKBP15‐2, inhibiting its peptidyl‐prolyl cis‐trans isomerase activity and thereby increasing A. thaliana susceptibility to P. capsici (Fan et al. 2018). Additionally, PcAVR3a12 targets the negative regulator of plant immunity, cinnamyl alcohol dehydrogenase 7 (CAD7), and enhances its stability. This interaction suppresses multiple defence responses, including INF1‐induced cell necrosis, callose deposition, reactive oxygen species (ROS) accumulation, and WRKY33 transcription, thereby increasing disease susceptibility in tobacco (Li et al. 2019). PcRxLR25 enhances host susceptibility by suppressing receptor‐like cytoplasmic kinase class VII (RLCK‐VII) proteins such as Botrytis‐induced kinase 1 (BIK1), PBS1‐like kinase 8 (PBL8), and PBL17, which are key components of early PTI, thereby facilitating pathogen infection (Liang et al. 2021). The effector AVRvnt1 from P. infestans targets potato glycerate 3‐kinase (GLYK), inhibiting energy metabolism and promoting GLYK degradation via the proteasome (Gao et al. 2020; Mondal 2021). Crystal structure analysis shows AVRvnt1 has low similarity to typical RXLR effectors like AVR3a, with AVRvnt1 comprising four α‐helices but lacking a conserved WY motif (Figure S4AC). This raises questions about how it stabilises its structure for virulence. Structural analysis of the AVRvnt1‐GLYK complex reveals that GLYK forms a dimer, with each monomer binding to AVRvnt1 through critical salt bridges and hydrophobic interactions (Figure S4E). Salt bridges between K104, R109, and K116 in AVRvnt1 and D146, D119, and D120 in GLYK, and the side chain of Y84 in AVRvnt1 also form a hydrophobic bond with Y122 in GLYK, suggesting their key role in the interaction (Figure S4E). Further research is needed to pinpoint the specific sites crucial for this complex formation.

The Pi04314 effector from P. infestans manipulates host cell processes to facilitate infection. It interacts with three isoforms of the host protein phosphatase 1 catalytic (PP1c) subunit and suppresses the transcription of JA and SA genes, crucial for systemic acquired resistance (Boevink et al. 2016). The R/KVXF motif in Pi04314 is crucial for binding and translocating with PP1c‐1. Structural analysis shows Pi04314 shares high similarity and a conserved hydrophobic core with AVR3a and AVR3a11 (Figure S4B–D). The C‐termini flexible region of Pi04314, including the R/KVXF motif, is vital for PP1c binding, with side chains of H132, K137, K138, N134, and N135 forming salt bridges or hydrogen bonds with D238, D240, E165, and D164 of PP1c (Figure S4F). V139 and F141 of R/KVXF engage in hydrophobic interactions with L241 of PP1c, further stabilising the complex (Figure S4F). This structural flexibility in the C‐termini of oomycete effectors like Pi04314, AVR3a, and PexRD54 underlies their functional diversity and the importance of the R/KVXF motif. P. infestans effectors, such as Pi22926 and PexRD2, suppress the host's mitogen‐activated protein kinase (MAPK) pathway, a key regulator of immunity (King et al. 2014; Ren et al. 2019; Wang et al. 2018). Structural analysis of PexRD2 has revealed typical features of RXLR effectors and a potential oligomerisation through its conserved WY motif (Boutemy et al. 2011). PexRD2 also has a unique 16‐residue insertion in loop3 compared to AVR3a and AVR3a11, whose role in suppressing plant immunity remains to be investigated.

Phytophthora sojae effectors manipulate host stress‐response enzymes to increase plant susceptibility and aid pathogen invasion. For instance, PsAVR1d competes with soybean E2 ubiquitin‐conjugating enzyme (GmE2s) for interaction with E3 ubiquitin ligase GmPUB13, reducing its activity and preventing degradation of the susceptibility factor GmPUB13, thereby enhancing P. sojae infection (Hou et al. 2023; Lin et al. 2021). Structural analysis of the PsAvr1d‐GmPUB13 U‐box complex has shown that PsAvr1d, like Avr3a and Avr3a11, has a conserved WY motif and high structural similarity (Lin et al. 2021). It is believed that PsAvr1d blocks GmPUB13's function by binding to its GmE2s interface, particularly through the insertion of PsAvr1d's F90 into a hydrophobic groove on GmPUB13 formed by residues P264, I265, W290 and P29957 (Lin et al. 2021). Substitutions of these residues weaken the PsAvr1d–GmPUB13 interaction, emphasising their role in complex stability (Lin et al. 2021).

PsAvh238 and PsAvh240 are other P. sojae effectors that facilitate pathogen invasion by targeting stress‐response enzymes. In soybean, PsAvh238 enhances plant susceptibility and pathogen infection by targeting the key enzyme 1‐aminocyclopropane‐1‐carboxylate synthase (ACS), promoting 26S proteasome‐mediated degradation of GmACS1, and thereby suppressing ethylene‐mediated immune responses (Yang et al. 2019). Specifically, the 82–122 amino acid region of PsAvh238 mediates its interaction with GmACS1, inhibiting GmACS1‐dependent ethylene synthesis (Yang et al. 2019). Although the crystal structure of the PsAvh240–GmAP1 complex has not yet been resolved, the solved structure of PsAvh240 alone provides important clues to its functional mechanism, particularly highlighting the role of its N‐terminal α1 and α2 helices (Guo et al. 2019). For instance, PsAvh240 enhances host susceptibility by interacting with aspartic protease GmAP1 through these two helices, thereby blocking its secretion into the apoplast and impairing its defensive function (Guo et al. 2019). Structural analysis of PsAvh240 has revealed that it comprises six α‐helices, two WY motifs, and a conserved hydrophobic core (Guo et al. 2019). Its N‐terminal double helix contains a positively charged region (Arg68, Arg71, Lys75, Lys80, Lys85, Lys91) that interacts with the negatively charged phosphatidylinositol 4‐phosphate on the cell membrane, aiding membrane localisation (Guo et al. 2019; Gronnier et al. 2017; Simon et al. 2016). PsAvh240 forms homodimers through interactions involving D156, Y159, Y177, Y180, and L184 of its WY motif, with a Y180A substitution disrupting this dimerisation and diminishing P. sojae's pathogenicity, underscoring the crucial role of PsAvh240 dimerisation in its virulence function. This suggests that dynamic monomer‐dimer transitions might enable diverse localisations and functions of oomycete effectors, warranting further investigation.

Some effectors mimic host enzymes and compete for control over host signalling pathways. The plant enzyme phosphatase 2A (PP2A) is essential for regulating signalling pathways that respond to pathogen invasion, with effectors from diverse pathogens, including Pseudomonas syringae (AvrE), Agrobacterium tumefaciens (DspA/E), H. arabidopsidis (HaRxL23), and P. infestans (PiPSR2) known to manipulate the activity of this enzyme (Jin et al. 2016; Li et al. 2023; Segonzac et al. 2014; Siamer et al. 2014). The P. infestans effector PiPSR2 mimics the PP2A core subunit β, recruits the scaffold subunit A and catalytic subunit C, and inhibits PP2A activity, impeding plant defences (Li et al. 2023). PSR2 also prevents PDF1 from forming the holoenzyme with the β subunit ATB'γ. Structural analysis of PSR2 monomers and their interaction with PDF1 has revealed significant conformational changes in the LWY2 and LWY3 motifs of PSR2 during the ‘capture’ of PDF1, highlighting a dynamic transition from an unbound to a bound state as PSR2 engages the N‐terminus of PDF1 (Li et al. 2023). The side chains of K211, K215, K219 and Q221 in LWY2‐L2 of PSR2 form hydrogen bonds or salt bridges with A135, E163, D209, Q173, and Q170 of PDF1. Similarly, K299, Y303, E307 and D310 in LWY3‐L1 of PSR2 interact with E98, R181, Q215 and R256 of PDF1. Key sites in LWY3‐α3 of PSR2, including R256, E260, Q263 and K267, form a clamp‐like structure stabilising the PSR2–PDF1 complex. Mutations at R256 and Q263 of PSR2 significantly weaken its interaction with PDF1 (Li et al. 2023). Moreover, the effector PSR2^{R256A/E260A/Q263A} mutant nearly eliminates its capacity to bind PDF1, underscoring the vital importance of the LWY3‐α3 motif in PDF1 interaction (Li et al. 2023). Other RXLR effectors in P. infestans , such as PITG_15142, also ‘hijack’ the host's PP2A core enzyme. PITG_15142 has a WY1‐(LWY)4 structure, with its WY1‐LWY2 highly homologous to PSR2's (L)WY2‐LWY363 (Li et al. 2023). The key interaction sites with PDF1 are conserved in PITG_15142, and mutations similar to those in PSR2 result in a loss of interaction capability of PITG_15142 with PDF1. This suggests oomycetes secrete multiple redundant effectors to undermine host immune recognition, aiding in plant colonisation. This redundancy likely evolved to help oomycetes adapt to varying environments and plant defences, giving them a competitive advantage.

5. Molecular Mechanisms by Which RXLR Effectors Target Plant Immunity

5.1. Conclusions and Prospects

Oomycetes infect a wide range of crop species, causing significant economic damage and yield losses (Derevnina et al. 2016; Fones et al. 2020; Yang et al. 2024). Despite their agricultural significance, the molecular mechanisms underlying oomycete infection and structural aspects of their effectors remain poorly understood, hindering the development of broad‐spectrum resistant crop varieties and effective disease management strategies. This review highlights the structural basis of oomycete RXLR effectors and their roles in the evolutionary arms race between pathogens and plants. While some structural information has emerged regarding oomycete RXLR effectors and their interactions with plant proteins, the molecular details of how these effectors suppress plant immunity remain largely unexplored. Obtaining high‐resolution structural insights into effector–host target complexes is critical for understanding how structurally conserved effectors can exhibit functional diversity. Such insights are also critical for developing the design of novel control strategies. For instance, the RXLR motif is typically associated with effector delivery into plant cells, as observed in effectors including AVR3a, Pi09216, Pi04097 and Pi21388 (Wawra et al. 2017; Whisson et al. 2007; Xu et al. 2025). Proteolytic cleavage of the RXLR motif of these effectors appears to facilitate effector secretion and translocation, and in some cases, the N‐terminal is acetylated following cleavage, as reported for Avr3a (Wawra et al. 2017; Xu et al. 2025). This suggests that the RXLR motif acts as a conserved protease recognition site, although the mechanism by which cleaved effectors translocate from hyphae to plant cells remains unknown (Wawra et al. 2017; Xu et al. 2025). Structural analyses further indicate that the RXLR motif potentially contributes to effector stability (Boutemy et al. 2011; Wawra et al. 2017; Wood et al. 2020). The WY motifs of effectors such as PsAvh240 and PiSFI3 are essential for their dimerisation, subcellular localisation, and virulence (Guo et al. 2019; He et al. 2019). Similarly, the flexible C‐terminal regions of effectors like PexRD54, AVR3a and Pi04314 contribute to immune suppression, though their specific mechanistic pathways may differ. Deciphering these structural features could enable the development of specific molecular binders or engineering plant R proteins that target conserved WY motifs, providing an approach to managing oomycete‐induced diseases (Jones et al. 2024; Li et al. 2022).

Plant R proteins recognise oomycete effectors and trigger immune responses. To evade this, effectors may (1) lose the ability to interact with R proteins through deletions, mutations, or frameshifts; or (2) obstruct recognition via steric hindrance from repeated WY and LWY motifs. Given these evasion strategies, advanced biotechnological approaches like protein engineering, genome editing, and host‐induced gene silencing (HIGS) are promising for controlling oomycete diseases without harming crop yield.

Protein engineering involves modifying immune receptors to alter or expand their recognition profiles. A notable example is the modification of the PBS1 receptor in A. thaliana to recognise AvrRpt2 by exploiting differences in cleavage sites between AvrPphB and AvrRpt2 (Kim et al. 2016). Similarly, in rice, researchers have developed disease‐resistant varieties like Pikp‐1, Pikm‐1 and RGA5 by modifying immune receptors based on the structural features of their HMA domains and those of Magnaporthe oryzae effectors (Bentham et al. 2023; Cesari et al. 2022; Liu et al. 2021; Zhang et al. 2024). Gene editing, particularly with CRISPR/Cas9, shows great promise for breeding disease‐resistant crops. For example, knocking down the susceptibility gene AtERF019 in tobacco increased resistance to black shank disease (Lu et al. 2020). Similarly, deleting the immune response inhibitor TcNPR3 in cacao improved resistance to black pod disease caused by Phytophthora tropicalis (Fister et al. 2018). HIGS is an effective strategy for controlling crop diseases (Govindarajulu et al. 2015; Jin et al. 2024). For example, expressing inverted repeats of HAM34 and CES1 genes in lettuce suppressed Bremia lactucae growth and sporulation (Govindarajulu et al. 2015). PrimeRoot technology is another novel method for controlling crop diseases. PrimeRoot technology integrates DNA fragments encoding immune receptors into crop genomes to create disease‐resistant lines. For example, inserting the PigmR gene fused with the OsAct1 promoter into rice significantly enhanced its resistance to rice blast disease (Sun et al. 2024). Upstream open reading frame (uORF) engineering is another critical strategy for enhancing crop immunity. In this context, researchers engineered an immune‐responsive TBF1 cassette by fusing a pathogen‐inducible promoter with two uORFs (uORFsTBF1) derived from the immune regulator TBF1 and driving the expression of the A. thaliana immune gene NPR1 (Xu et al. 2017). Transgenic rice lines carrying this cassette exhibited significantly enhanced resistance to Xanthomonas oryzae pv. oryzae. In a separate study, oomycete pathogens were shown to secrete conserved kinase effectors that stably bind to and phosphorylate the aquaporin PIP2;7, inducing its degradation and promoting host susceptibility. To counter this mechanism, researchers developed a uORFACD11‐responsive cassette to express a phosphorylation‐resistant PIP2;7^S273A/S276A variant (Zhu et al. 2025). Transgenic lines expressing this variant displayed enhanced resistance to oomycete pathogens without compromising drought tolerance. These advancements offer promising avenues for developing more disease‐resistant crop varieties.

Identifying novel immune receptors or core signalling proteins is crucial for developing effective plant disease control strategies. High‐throughput techniques like genome‐wide association studies (GWAS) based on pan‐genome analysis can pinpoint key genetic components for disease resistance (Demirjian et al. 2023; Serrie et al. 2025; Gai et al. 2023). For instance, GWAS identified potato late blight resistance genes Rpi‐amr1, Rpi‐amr1e, Rpi‐amr3 and Rpi‐amr4 from Solanum nigrum , which target P. infestans effectors (Lin et al. 2023; Witek et al. 2021). Cloning these genes provides valuable resources for breeding late blight‐resistant potato varieties, essential for food security. Understanding the complex molecular mechanisms of oomycete–plant interactions and the structural operation of oomycete effectors is crucial for developing novel breeding techniques. By dissecting these processes, researchers can design crop varieties with enhanced resistance to oomycete diseases and develop sustainable plant protection strategies. This knowledge enables the identification of molecular targets for genetic manipulation, creating environmentally friendly solutions that reduce reliance on chemical pesticides. Insights into oomycete effectors and their functions in host plants can revolutionise plant breeding and protection, leading to more robust and sustainable agricultural practices.

Author Contributions

A. X. Wang and J. F. Liu conceived the content and organisation of this review. Y. Liu, Y. Y. Zheng, X. R. Zhou and H. Ghanizadeh contributed equally to the composition and preparation of this review. All authors drafted and prepared figures, revised and approved the final version of this manuscript.

Conflicts of Interest

The authors declare no conflicts of interest.

Supporting information

Figure S1: Sequence alignment of RxLR effectors. Identical and conserved amino acid residues are boxed in red.

Data S1: mpp70138‐sup‐0002‐FigureS1.tif.

Data S2: mpp70138‐sup‐0003‐FigureS1.tif.

Figure S2:Oomycete effectors regulate host autophagy and immunity. The targeting of host autophagy‐related proteins by oomycete effectors regulates plant autophagy. (A) The effector PpAvh195 from Phytophthora parasitica interacts with ATG8s, inhibiting the fusion of lysosome‐like structures with vesicles, thereby suppressing autophagy in Arabidopsis thaliana and increasing its disease susceptibility. (B) The Phytophthora infestans effector PexRD54 inhibits multiple autophagy‐related proteins, including StJoka2, Rab8a and StATG8CL, impeding the formation of defence‐related autophagosomes and enhancing disease susceptibility in potato. (C) The three‐dimensional structure of PexRD54 consists of five repeated WY motifs, each represented by a different colour: blue, rose, bright green, cyan, olive and brown. (D) The structural complex of StATG8CL with the C‐termini region of PexRD54, depicted with StATG8CL in fluorescent green and the C‐termini of PexRD54 in brown.

Figure S3: Oomycete effectors regulate the RNA transcription process in plants. (A) Oomycete effectors regulate the transcription of related genes through transcription regulators, thereby influencing plant growth and immunity. (B) effectors enhance plant susceptibility by interacting with transcription factors or impeding the binding of transcription factors to the promoter regions of defence genes. (C) Oomycete effectors bind to double‐stranded RNA‐binding proteins (DRBs), thereby inhibiting plant RNA interference (RNAi).

Figure S4: Structure of RXLR effectors and their complex with plant target proteins. (A) Structure of AVRvnt1 (navy). (B) The WY motif includes W95 and Y118, which is shown in the structure of Pi03414. (C) The structure of Pi03414 was compared with Avr3a (purple). (D) The structural alignment of Avr3a11 (green) and Pi03414 (yellow). (E) The complex structure of AVRvnt1 (shown as light blue and navy) bound to GLYK (coloured with violet and wheat). The dashed box indicates the interaction of AVRvnt1 and GLYK. (F) The complex structure of Pi03414‐PP1c and the interaction between the C‐termini of Pi03414 and PP1c were shown in a dashed box, Pi03414 was marked with yellow and pink and PP1c was shown as light green and orange.

Liu, Y. , Zheng Y. Y., Zhou X. R., et al. 2025. “Structural Insights Into the Role of RxLR Effectors in the Arms Race Between Oomycetes and Plants.” Molecular Plant Pathology 26, no. 9: e70138. 10.1111/mpp.70138.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.