A rationally designed JAZ subtype-selective agonist of jasmonate perception
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ABSTRACT:
ORGANISM(S): Arabidopsis thaliana
PROVIDER: GSE110858 | GEO | 2018/08/05
REPOSITORIES: GEO
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Project description:A rationally designed JAZ subtype-selective agonist of jasmonate perception
| PRJNA434702 | ENA
Project description:The phytohormone 7-iso-(+)-jasmonoyl-L-isoleucine (JA-Ile) mediates plant defense responses against herbivore and pathogen attack, and thus increases plant resistance against foreign invaders. However, JA-Ile also causes growth inhibition; and therefore JA-Ile is not a practical chemical regulator of plant defense responses. Here, we describe the rational design and synthesis of a small molecule agonist that can upregulate defense-related gene expression and promote pathogen resistance at concentrations that do not cause growth inhibition in Arabidopsis. By stabilizing interactions between COI1 and JAZ9 and JAZ10 but no other JAZ isoforms, the agonist leads to formation of JA-Ile co-receptors that selectively activate the JAZ9-EIN3/EIL1-ORA59 signaling pathway. The design of a JA-Ile agonist with high selectivity for specific protein subtypes may help promote the development of chemical regulators that do not cause a tradeoff between growth and defense.
| S-EPMC6128907 | biostudies-literature
Project description:We report the development of subtype selective ligands into plant hormone jasmonate co-receptor COI1-JAZ. Plant hormone jasmonoyl isoleucine and the structural mimic natural product coronatine has non-selective affinity with 13 species of COI1-JAZ co-receptors in Arabidopsis thaliana to cause bath of bacterial defense and growth inhibition. Some subtype selective ligands were developed by our chemical screening and activated the part of whole jasmonate signaling. To examine the mode-of-action of the subtype selective ligand, gene expression profiles of WT and jaz9 mutant treated with mock or with coronatine (2) and subtype selective ligands (2e and 12) was performed using the RNA-seq. The subtype selective ligand induced partial activation of jasmonate signaling to cause defense responses against bacterial pathogen without growth inhibition.
2024-09-08 | GSE184730 | GEO
Project description:Jasmonates are a family of plant hormones that regulate plant growth, development and responses to stress. The F-box protein CORONATINE INSENSITIVE 1 (COI1) mediates jasmonate signalling by promoting hormone-dependent ubiquitylation and degradation of transcriptional repressor JAZ proteins. Despite its importance, the mechanism of jasmonate perception remains unclear. Here we present structural and pharmacological data to show that the true Arabidopsis jasmonate receptor is a complex of both COI1 and JAZ. COI1 contains an open pocket that recognizes the bioactive hormone (3R,7S)-jasmonoyl-l-isoleucine (JA-Ile) with high specificity. High-affinity hormone binding requires a bipartite JAZ degron sequence consisting of a conserved ?-helix for COI1 docking and a loop region to trap the hormone in its binding pocket. In addition, we identify a third critical component of the jasmonate co-receptor complex, inositol pentakisphosphate, which interacts with both COI1 and JAZ adjacent to the ligand. Our results unravel the mechanism of jasmonate perception and highlight the ability of F-box proteins to evolve as multi-component signalling hubs.
| S-EPMC2988090 | biostudies-literature
Project description:Jasmonates (JAs) are plant hormones with crucial roles in development and stress resilience. They activate MYC transcription factors by mediating the proteolysis of MYC inhibitors called JAZ proteins. In the absence of JA, JAZ proteins bind and inhibit MYC through the assembly of MYC-JAZ-Novel Interactor of JAZ (NINJA)-TPL repressor complexes. However, JAZ and NINJA are predicted to be largely intrinsically unstructured, which has precluded their experimental structure determination. Through a combination of biochemical, mutational, and biophysical analyses and AlphaFold-derived ColabFold modeling, we characterized JAZ-JAZ and JAZ-NINJA interactions and generated models with detailed, high-confidence domain interfaces. We demonstrate that JAZ, NINJA, and MYC interface domains are dynamic in isolation and become stabilized in a stepwise order upon complex assembly. By contrast, most JAZ and NINJA regions outside of the interfaces remain highly dynamic and cannot be modeled in a single conformation. Our data indicate that the small JAZ Zinc finger expressed in Inflorescence Meristem (ZIM) motif mediates JAZ-JAZ and JAZ-NINJA interactions through separate surfaces, and our data further suggest that NINJA modulates JAZ dimerization. This study advances our understanding of JA signaling by providing insights into the dynamics, interactions, and structure of the JAZ-NINJA core of the JA repressor complex.
| S-EPMC10721472 | biostudies-literature
Project description:By using rational design, antibody fragments (Fabs) that mimic thrombopoietin (TPO) were created. A peptide with cMpl receptor-binding capability was grafted into different complementarity-determining regions of a fully human Fab scaffold. Functional presentation of the peptide was optimized by using phage display and cell-based panning. Select antibodies and fragments containing two grafted peptides were assayed for their ability to stimulate the cMpl receptor in vitro. Several candidates demonstrated agonist activity in an in vitro cMpl receptor signaling reporter assay, including Fab59, which was estimated to be equipotent to TPO. Fab59 additionally was able to effectively stimulate platelet production in normal mice. These rationally designed mimetic Fabs may provide a therapeutic intervention for thrombocytopenia while avoiding the potential generation of neutralizing antibodies to endogenous TPO. Furthermore, this study demonstrates a method by which short-lived linear peptides with binding activity may be converted to more stable and potent agonists capable of activating cell surface receptors.
| S-EPMC1599960 | biostudies-literature
Project description:We have investigated the genome regulatory network that controls responses to the hormone jasmonate in seedlings. There is much interest currently in understanding the systems-level actions of transcription factors. However, such studies can provide much greater biological insight if set in the context of the signal transduction pathway that initiates gene expression changes and the downstream organismal phenotypes they control. We have generated an integrated framework of the response to jasmonate that spans from signal perception and transduction, through activity of master and secondary-regulatory transcription factors, to gene expression outputs and chromatin remodelling. We make use of genome-wide target maps for hundreds of transcription factors, dynamic histone modification analysis, global proteome and phosphoproteome analyses, massively multiplexed protein-protein interactome data and time series transcriptome analysis. This enables us to predict previously unknown components of the jasmonate regulatory mechanism and validate them through targeted mutant studies. The result is a comprehensive understanding of how a plant hormone remodels cellular function and plant behaviour.
2020-03-19 | PXD013592 | Pride
Project description:JAZ genes are negative regulators of jasmonate responses with a dual function as repressors of transcription factors and co-receptors, together with COI1, of the hormone jasmonoyl-isoleucine (JA-Ile). This family has been mainly studied in angiosperms, where high gene redundancy hinders the characterization of a complete depletion of JAZ function. Moreover, the recent discovery that JA-Ile is not the sole COI1/JAZ ligand in land plants, as dn-OPDA is the bioactive ligand in Marchantia polymorpha, underscores the importance of studying JAZ co-receptors in bryophytes. Here we exploited the low gene redundancy of the liverwort Marchantia polymorpha to characterize the function of the single MpJAZ in this early-divergent plant lineage. We demonstrate that MpJAZ is the ortholog of AtJAZ and acts as a repressor of dinor-OPDA responses in Marchantia. Mpjaz mutants show a dwarf phenotype and severe developmental defects related to growth inhibition, consistent with a constitutive activation of the dinor-OPDA pathway and the overaccumulation of both dinor-OPDA and its precursor OPDA. The expression of AtJAZ3 in Mpjaz complements MpJAZ repressor function, indicating that JAZ function is conserved across land plants. However, AtJAZ3 is unable to form co-receptor complexes with MpCOI1 and dn-OPDA, which evidences that the Jas domain, and not only COI1, determines ligand specificity.
2018-11-10 | GSE118149 | GEO
Project description:Jasmonate is an essential phytohormone involved in plant development and stress responses. Jasmonate perception occurs through the COI nuclear receptor allowing to target the JAZs repressors for degradation by the 26S proteasome. Consequently, repressed transcription factors are released and expression of JA-responsive genes is induced. In rice, three OsCOI genes have been identified, OsCOI1a and the closely related OsCOI1b homolog, and OsCOI2. While a role for OsCOI-1a and -1b genes was previously established in plant defense or leaf senescence, evidence for an important role of OsCOI2 in plant development, jasmonate-signaling and defence emerged only recently. To decipher the role of OsCOI2 in regulating jasmonate responses, we used rice mutant lines, edited both in the OsCOI1a and OsCOI1b genes, or in the OsCOI2 gene. Rice roots from WT and oscoi lines were treated by jasmonate to establish the molecular responses of each line, at the transcriptomic and metabolomic levels. RNA-seq data indicate that OsCOI2 is the main actor of the large transcriptional reprogramming observed after a JA challenge in rice roots. A series of transcription factors with an OsCOI2-dependent expression was identified, including transcription factors known to have a role in root development or stress response. An OsCOI2-dependent expression was detected for genes involved in specific processes or pathways such as photosynthesis, cell-growth and secondary metabolite biosynthesis (phenylpropanoids and diterpene phytoalexins). Functional redundancy between OsCOI1a/b and OsCOI2 can be shown for some genes, even if a lower response usually occurred in oscoi2 plants compared to oscoi1ab plants. Metabolic data revealed a shift from the primary metabolism to the secondary metabolism that is mainly OsCOI2-dependent. Differential accumulation of oryzalexins was also observed in oscoi lines.These data validate the major role of OsCOI2 in JA responses in rice roots. OsCOI2 is the major regulator of specialized metabolic pathways related to development and production of secondary metabolites. This study suggests that OsCOI2 controls the growth-defense trade-off in response to JA.
2024-09-17 | GSE262371 | GEO
Project description:A single JAZ repressor controls the jasmonate pathway in Marchantia polymorpha
| PRJNA484711 | ENA