scholarly journals The allelic rice immune receptor Pikh confers extended resistance to strains of the blast fungus through a single polymorphism in the effector binding interface

2020 ◽  
Author(s):  
Juan Carlos De la Concepcion ◽  
Josephine H. R. Maidment ◽  
Apinya Longya ◽  
Gui Xiao ◽  
Marina Franceschetti ◽  
...  
Keyword(s):  
Immune Responses ◽  
Rice Blast ◽  
Immune Recognition ◽  
Immune Receptor ◽  
Immune Receptors ◽  
Pathogen Effectors ◽  
Binding Interface ◽  
Recognition Specificity ◽  
Blast Fungus ◽  
Effector Recognition

AbstractArms race co-evolution drives rapid adaptive changes in pathogens and in the immune systems of their hosts. Plant intracellular NLR immune receptors detect effectors delivered by pathogens to promote susceptibility, activating an immune response that halts colonization. As a consequence, pathogen effectors evolve to escape immune recognition and are highly variable. In turn, NLR receptors are one of the most diverse protein families in plants, and this variability underpins differential recognition of effector variants. The molecular mechanisms underlying natural variation in effector recognition by NLRs are starting to be elucidated. The rice NLR pair Pik-1/Pik-2 recognizes AVR-Pik effectors from the blast fungus Magnaporthe oryzae, triggering immune responses that limit rice blast infection. Allelic variation in a heavy metal associated (HMA) domain integrated in the receptor Pik-1 confers differential binding to AVR-Pik variants, determining resistance specificity. Previous mechanistic studies uncovered how a Pik allele, Pikm, has extended recognition to effector variants through a specialized HMA/AVR-Pik binding interface. Here, we reveal the mechanistic basis of extended recognition specificity conferred by another Pik allele, Pikh. A single residue in Pikh-HMA increases binding to AVR-Pik variants, leading to an extended effector response in planta. The crystal structure of Pikh-HMA in complex with an AVR-Pik variant confirmed that Pikh and Pikm use a similar molecular mechanism to extend their pathogen recognition profile. This study shows how different NLR receptor alleles functionally converge to extend recognition specificity to pathogen effectors.Author SummaryPlant pathogens constantly evolve to overcome immune defences and successfully colonize hosts, resulting in some of the most devastating diseases that affect global food production. To defend themselves, plants have evolved a sophisticated immune system that recognizes the presence of different pathogens and triggers immune responses to stop their spread. How plant immune receptors achieve extended recognition to specific pathogen strains and the molecular details of this recognition are just starting to be understood.In this study, we characterize how an allele of a rice immune receptor achieves a broad-spectrum recognition to effectors from the rice blast fungus. We found that this receptor has evolved a single change that alters the way it binds to different effector variants. This change increases binding affinity to these variants and this is ultimately translated to immune recognition. Interestingly, a different rice immune receptor allele also achieves broad-spectrum effector recognition in a similar way. Therefore, different immune receptor alleles can converge on a similar mechanism to achieve extended recognition to pathogen effectors.This knowledge has the potential to help to the rational design of plant immune receptors with bespoke resistance to some of the most destructive pathogens. A long-term goal in plant biotechnology.

scholarly journals The allelic rice immune receptor Pikh confers extended resistance to strains of the blast fungus through a single polymorphism in the effector binding interface

2021 ◽  
Vol 17 (3) ◽  
pp. e1009368
Author(s):  
Juan Carlos De la Concepcion ◽  
Josephine H. R. Maidment ◽  
Apinya Longya ◽  
Gui Xiao ◽  
Marina Franceschetti ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Allelic Variation ◽  
Immune Recognition ◽  
In Planta ◽  
Pathogen Effectors ◽  
Binding Interface ◽  
Recognition Specificity ◽  
Blast Fungus ◽  
Resistance Specificity ◽  
Mechanistic Basis

Arms race co-evolution drives rapid adaptive changes in pathogens and in the immune systems of their hosts. Plant intracellular NLR immune receptors detect effectors delivered by pathogens to promote susceptibility, activating an immune response that halts colonization. As a consequence, pathogen effectors evolve to escape immune recognition and are highly variable. In turn, NLR receptors are one of the most diverse protein families in plants, and this variability underpins differential recognition of effector variants. The molecular mechanisms underlying natural variation in effector recognition by NLRs are starting to be elucidated. The rice NLR pair Pik-1/Pik-2 recognizes AVR-Pik effectors from the blast fungus Magnaporthe oryzae, triggering immune responses that limit rice blast infection. Allelic variation in a heavy metal associated (HMA) domain integrated in the receptor Pik-1 confers differential binding to AVR-Pik variants, determining resistance specificity. Previous mechanistic studies uncovered how a Pik allele, Pikm, has extended recognition to effector variants through a specialized HMA/AVR-Pik binding interface. Here, we reveal the mechanistic basis of extended recognition specificity conferred by another Pik allele, Pikh. A single residue in Pikh-HMA increases binding to AVR-Pik variants, leading to an extended effector response in planta. The crystal structure of Pikh-HMA in complex with an AVR-Pik variant confirmed that Pikh and Pikm use a similar molecular mechanism to extend their pathogen recognition profile. This study shows how different NLR receptor alleles functionally converge to extend recognition specificity to pathogen effectors.

scholarly journals Design of a new effector recognition specificity in a plant NLR immune receptor by molecular engineering of its integrated decoy domain

2021 ◽  
Author(s):  
Stella Cesari ◽  
Yuxuan Xi ◽  
Nathalie Declerck ◽  
Véronique Chalvon ◽  
Léa Mammri ◽  
...  
Keyword(s):  
Immune Responses ◽  
Crop Protection ◽  
Molecular Engineering ◽  
Future Research ◽  
Pathogen Effectors ◽  
Recognition Specificity ◽  
Heterologous System ◽  
Binding Surface ◽  
Engineering Strategy ◽  
Effector Recognition

SUMMARYPlant nucleotide-binding and leucine-rich repeat domain proteins (NLRs) are immune sensors that specifically recognize pathogen effectors and induce immune responses. Designing artificial NLRs with new effector recognition specificities is a promising prospect for sustainable, knowledge-driven crop protection. However, such strategies are hampered by the complexity of NLR function. Here, we tested whether molecular engineering of the integrated decoy domain (ID) of an NLR could extend its recognition spectrum to a new effector. To this aim, we relied on the detailed molecular knowledge of the recognition of distinct Magnaporthe oryzae MAX (Magnaporthe AVRs and ToxB-like) effectors by the rice NLRs RGA5 and Pikp-1. For both NLRs, effector recognition involves physical binding to their HMA (Heavy Metal-Associated) IDs. However, AVR-PikD, the effector recognized by Pikp-1, binds to a completely different surface of the HMA domain compared to AVR-Pia and AVR1-CO39, recognized by RGA5. By introducing into the HMA domain of RGA5 the residues of the Pikp-1 HMA domain involved in AVR-PikD binding, we created a high-affinity binding surface for this new effector. In the Nicotiana benthamiana heterologous system, RGA5 variants carrying this engineered binding surface still recognize AVR-Pia and AVR1-CO39, but also perceive the new ligand, AVR-PikD, resulting in the activation of immune responses. Therefore, our study provides a proof of concept for the design of new effector recognition specificities in NLRs through molecular engineering of IDs. However, it pinpoints significant knowledge gaps that limit the full deployment of this NLR-ID engineering strategy and provides hypotheses for future research on this topic.

scholarly journals Rice blast resistance-inducing mechanisms via effector recognition by NLR immune receptors

2016 ◽  
Vol 82 (4) ◽  
pp. 296-300 ◽  
Author(s):  
H. SAITOH ◽  
H. KANZAKI ◽  
K. FUJISAKI ◽  
H. TAKAGI ◽  
K. YOSHIDA ◽  
...  
Keyword(s):  
Rice Blast ◽  
Blast Resistance ◽  
Rice Blast Resistance ◽  
Immune Receptors ◽  
Effector Recognition

scholarly journals Structural basis of pathogen recognition by an integrated HMA domain in a plant NLR immune receptor

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
A Maqbool ◽  
H Saitoh ◽  
M Franceschetti ◽  
CEM Stevenson ◽  
A Uemura ◽  
...  
Keyword(s):  
Nicotiana Benthamiana ◽  
Rice Blast ◽  
Plant Pathogens ◽  
Rice Cultivar ◽  
Blast Disease ◽  
Structural Basis ◽  
Immune Receptor ◽  
Immune Receptors ◽  
Direct Recognition

Plants have evolved intracellular immune receptors to detect pathogen proteins known as effectors. How these immune receptors detect effectors remains poorly understood. Here we describe the structural basis for direct recognition of AVR-Pik, an effector from the rice blast pathogen, by the rice intracellular NLR immune receptor Pik. AVR-PikD binds a dimer of the Pikp-1 HMA integrated domain with nanomolar affinity. The crystal structure of the Pikp-HMA/AVR-PikD complex enabled design of mutations to alter protein interaction in yeast and in vitro, and perturb effector-mediated response both in a rice cultivar containing Pikp and upon expression of AVR-PikD and Pikp in the model plant Nicotiana benthamiana. These data reveal the molecular details of a recognition event, mediated by a novel integrated domain in an NLR, which initiates a plant immune response and resistance to rice blast disease. Such studies underpin novel opportunities for engineering disease resistance to plant pathogens in staple food crops.

scholarly journals Protein engineering expands the effector recognition profile of a rice NLR immune receptor

2019 ◽  
Author(s):  
JC De la Concepcion ◽  
M Franceschetti ◽  
R Terauchi ◽  
S Kamoun ◽  
MJ Banfield
Keyword(s):  
Protein Engineering ◽  
Direct Interaction ◽  
In Planta ◽  
Pathogen Effectors ◽  
Binding Interface ◽  
Pathogen Effector ◽  
Integrated Domains ◽  
Effector Recognition

AbstractPlant NLR receptors detect pathogen effectors and initiate an immune response. Since their discovery, NLRs have been the focus of protein engineering to improve disease resistance. However, this has proven challenging, in part due to their narrow response specificity. Here, we used structure-guided engineering to expand the response profile of the rice NLR Pikp to variants of the rice blast pathogen effector AVR-Pik. A mutation located within an effector binding interface of the integrated Pikp-HMA domain increased the binding affinity for AVR-Pik variants in vitro and in vivo. This translates to an expanded cell death response to AVR-Pik variants previously unrecognized by Pikp in planta. Structures of the engineered Pikp-HMA in complex with AVR-Pik variants revealed the mechanism of expanded recognition. These results provide a proof-of-concept that protein engineering can improve the utility of plant NLR receptors where direct interaction between effectors and NLRs is established, particularly via integrated domains.

OsWRKY28, a PAMP-responsive transrepressor, negatively regulates innate immune responses in rice against rice blast fungus

2013 ◽  
Vol 82 (1-2) ◽  
pp. 23-37 ◽  
Author(s):  
Tetsuya Chujo ◽  
Koji Miyamoto ◽  
Takeo Shimogawa ◽  
Takafumi Shimizu ◽  
Yuko Otake ◽  
...  
Keyword(s):  
Immune Responses ◽  
Rice Blast ◽  
Rice Blast Fungus ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Blast Fungus

scholarly journals Distinct modes of derepression of an Arabidopsis immune receptor complex by two different bacterial effectors

2018 ◽  
Vol 115 (41) ◽  
pp. 10218-10227 ◽  
Author(s):  
Yan Ma ◽  
Hailong Guo ◽  
Lanxi Hu ◽  
Paula Pons Martinez ◽  
Panagiotis N. Moschou ◽  
...  
Keyword(s):  
Wrky Transcription Factor ◽  
Leucine Rich Repeat ◽  
Wrky Domain ◽  
Inactive State ◽  
Immune Receptors ◽  
Pathogen Effectors ◽  
Effector Recognition ◽  
Bacterial Effectors ◽  
Colicin E9 ◽  
Domain 4

Plant intracellular nucleotide-binding leucine-rich repeat (NLR) immune receptors often function in pairs to detect pathogen effectors and activate defense. The Arabidopsis RRS1-R–RPS4 NLR pair recognizes the bacterial effectors AvrRps4 and PopP2 via an integrated WRKY transcription factor domain in RRS1-R that mimics the effector’s authentic targets. How the complex activates defense upon effector recognition is unknown. Deletion of the WRKY domain results in an RRS1 allele that triggers constitutive RPS4-dependent defense activation, suggesting that in the absence of effector, the WRKY domain contributes to maintaining the complex in an inactive state. We show the WRKY domain interacts with the adjacent domain 4, and that the inactive state of RRS1 is maintained by WRKY–domain 4 interactions before ligand detection. AvrRps4 interaction with the WRKY domain disrupts WRKY–domain 4 association, thus derepressing the complex. PopP2-triggered activation is less easily explained by such disruption and involves the longer C-terminal extension of RRS1-R. Furthermore, some mutations in RPS4 and RRS1 compromise PopP2 but not AvrRps4 recognition, suggesting that AvrRps4 and PopP2 derepress the complex differently. Consistent with this, a “reversibly closed” conformation of RRS1-R, engineered in a method exploiting the high affinity of colicin E9 and Im9 domains, reversibly loses AvrRps4, but not PopP2 responsiveness. Following RRS1 derepression, interactions between domain 4 and the RPS4 C-terminal domain likely contribute to activation. Simultaneous relief of autoinhibition and activation may contribute to defense activation in many immune receptors.

scholarly journals Cross-reactivity of a rice NLR immune receptor to distinct effectors from the blast pathogen leads to partial disease resistance

2019 ◽  
Author(s):  
Freya A. Varden ◽  
Hiromasa Saitoh ◽  
Kae Yoshino ◽  
Marina Franceschetti ◽  
Sophien Kamoun ◽  
...  
Keyword(s):  
Immune Response ◽  
Disease Resistance ◽  
Effector Proteins ◽  
In Planta ◽  
Immune Receptor ◽  
Immune Receptors ◽  
Binding Interface ◽  
Pathogen Effector ◽  
Integrated Domains

ABSTRACTUnconventional integrated domains in plant intracellular immune receptors (NLRs) can directly bind translocated pathogen effector proteins to initiate an immune response. The rice immune receptor pairs Pik-1/Pik-2 and RGA5/RGA4 both use integrated heavy metal-associated (HMA) domains to bind the Magnaporthe oryzae effectors AVR-Pik and AVR-Pia, respectively. These effectors both belong to the MAX effector family and share a core structural fold, despite being divergent in sequence. How integrated domains maintain specificity of recognition, even for structurally similar effectors, has implications for understanding plant immune receptor evolution and function. Here we show that the rice NLR pair Pikp-1/Pikp-2 triggers an immune response leading to partial disease resistance towards the “mismatched” effector AVR-Pia in planta, and that the Pikp-HMA domain binds AVR-Pia in vitro. The HMA domain from another Pik-1 allele, Pikm, is unable to bind AVR-Pia, and does not trigger a response in plants. The crystal structure of Pikp-HMA bound to AVR-Pia reveals a different binding interface compared to AVR-Pik effectors, suggesting plasticity in integrated domain/effector interactions. This work shows how a single NLR can bait multiple pathogen effectors via an integrated domain, and may enable engineering immune receptors with extended disease resistance profiles.

scholarly journals Epigenetic dysregulation of immune-related pathways in cancer: bioinformatics tools and visualization

2021 ◽  
Author(s):  
Anders Berglund ◽  
Ryan M. Putney ◽  
Imene Hamaidi ◽  
Sungjune Kim
Keyword(s):  
Patient Outcome ◽  
Immune Responses ◽  
Cancer Cells ◽  
Immune Evasion ◽  
Epigenetic Regulation ◽  
Current Evidence ◽  
Immune Recognition ◽  
Bioinformatics Tools ◽  
Visualization Techniques ◽  
Cancer Bioinformatics

AbstractCancer immune evasion is one of the hallmarks of carcinogenesis. Cancer cells employ multiple mechanisms to avoid immune recognition and suppress antitumor immune responses. Recently, accumulating evidence has indicated that immune-related pathways are epigenetically dysregulated in cancer. Most importantly, the epigenetic footprint of immune-related pathways is associated with the patient outcome, underscoring the crucial need to understand this process. In this review, we summarize the current evidence for epigenetic regulation of immune-related pathways in cancer and describe bioinformatics tools, informative visualization techniques, and resources to help decipher the cancer epigenome.

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