McCourt P

References (16)

Title : Structural analysis of a hormone-bound Striga strigolactone receptor - Arellano-Saab_2023_Nat.Plants_9_883
Author(s) : Arellano-Saab A , Skarina T , Xu Z , McErlean CSP , Savchenko A , Lumba S , Stogios PJ , McCourt P
Ref : Nat Plants , 9 :883 , 2023
Abstract : Strigolactones (SLs) regulate many aspects of plant development, but ambiguities remain about how this hormone is perceived because SL-complexed receptor structures do not exist. We find that when SL binds the Striga receptor, ShHTL5, a series of conformational changes relative to the unbound state occur, but these events are not sufficient for signalling. Ligand-complexed receptors, however, form internal tunnels that posit an explanation for how SL exits its receptor after hydrolysis.
ESTHER : Arellano-Saab_2023_Nat.Plants_9_883
PubMedSearch : Arellano-Saab_2023_Nat.Plants_9_883
PubMedID: 37264151
Gene_locus related to this paper: strhe-ShHTL5

Title : A novel strigolactone receptor antagonist provides insights into the structural inhibition, conditioning, and germination of the crop parasite Striga - Arellano-Saab_2022_J.Biol.Chem_298_101734
Author(s) : Arellano-Saab A , McErlean CSP , Lumba S , Savchenko A , Stogios PJ , McCourt P
Ref : Journal of Biological Chemistry , :101734 , 2022
Abstract : Crop parasites of the Striga genera are a major biological deterrent to food security in Africa and are one of the largest obstacles to poverty alleviation on the continent. Striga seeds germinate by sensing small-molecule hormones, strigolactones (SLs), that emanate from host roots. Although SL receptors (ShHTLs) have been identified, discerning their function has been difficult because these parasites cannot be easily grown under laboratory conditions. Moreover, many Striga species are obligate outcrossers that are not transformable, hence not amenable to genetic analysis. By combining phenotypic screening with ShHTL structural information and hybrid drug discovery methods, we discovered a potent SL perception inhibitor for Striga, dormirazine. Structural analysis of this piperazine-based antagonist reveals a novel binding mechanism, distinct from that of known SLs, blocking access of the hormone to its receptor. Furthermore, dormirazine reduces the flexibility of protein-protein interaction domains important for receptor signaling to downstream partners. In planta, we show, via temporal additions of dormirazine, that SL receptors are required at a specific time during seed conditioning. This conditioning is essential to prime seed germination at the right time; thus, this SL-sensitive stage appears to be critical for adequate receptor signaling. Aside from uncovering a function for ShHTL during seed conditioning, these results suggest that future Ag-biotech solutions to Striga infestations will need to carefully time the application of antagonists to exploit receptor availability and outcompete natural SLs, critical elements for successful parasitic plant invasions.
ESTHER : Arellano-Saab_2022_J.Biol.Chem_298_101734
PubMedSearch : Arellano-Saab_2022_J.Biol.Chem_298_101734
PubMedID: 35181340
Gene_locus related to this paper: strhe-ShHTL7

Title : Three mutations repurpose a plant karrikin receptor to a strigolactone receptor - Arellano-Saab_2021_Proc.Natl.Acad.Sci.U.S.A_118_
Author(s) : Arellano-Saab A , Bunsick M , Al Galib H , Zhao W , Schuetz S , Bradley JM , Xu Z , Adityani C , Subha A , McKay H , de Saint Germain A , Boyer FD , McErlean CSP , Toh S , McCourt P , Stogios PJ , Lumba S
Ref : Proc Natl Acad Sci U S A , 118 : , 2021
Abstract : Uncovering the basis of small-molecule hormone receptors' evolution is paramount to a complete understanding of how protein structure drives function. In plants, hormone receptors for strigolactones are well suited to evolutionary inquiries because closely related homologs have different ligand preferences. More importantly, because of facile plant transgenic systems, receptors can be swapped and quickly assessed functionally in vivo. Here, we show that only three mutations are required to turn the nonstrigolactone receptor, KAI2, into a receptor that recognizes the plant hormone strigolactone. This modified receptor still retains its native function to perceive KAI2 ligands. Our directed evolution studies indicate that only a few keystone mutations are required to increase receptor promiscuity of KAI2, which may have implications for strigolactone receptor evolution in parasitic plants.
ESTHER : Arellano-Saab_2021_Proc.Natl.Acad.Sci.U.S.A_118_
PubMedSearch : Arellano-Saab_2021_Proc.Natl.Acad.Sci.U.S.A_118_
PubMedID: 34301902
Gene_locus related to this paper: arath-AtD14 , arath-KAI2.D14L

Title : Genome Sequence of Striga asiatica Provides Insight into the Evolution of Plant Parasitism - Yoshida_2019_Curr.Biol_29_3041
Author(s) : Yoshida S , Kim S , Wafula EK , Tanskanen J , Kim YM , Honaas L , Yang Z , Spallek T , Conn CE , Ichihashi Y , Cheong K , Cui S , Der JP , Gundlach H , Jiao Y , Hori C , Ishida JK , Kasahara H , Kiba T , Kim MS , Koo N , Laohavisit A , Lee YH , Lumba S , McCourt P , Mortimer JC , Mutuku JM , Nomura T , Sasaki-Sekimoto Y , Seto Y , Wang Y , Wakatake T , Sakakibara H , Demura T , Yamaguchi S , Yoneyama K , Manabe RI , Nelson DC , Schulman AH , Timko MP , dePamphilis CW , Choi D , Shirasu K
Ref : Current Biology , 29 :3041 , 2019
Abstract : Parasitic plants in the genus Striga, commonly known as witchweeds, cause major crop losses in sub-Saharan Africa and pose a threat to agriculture worldwide. An understanding of Striga parasite biology, which could lead to agricultural solutions, has been hampered by the lack of genome information. Here, we report the draft genome sequence of Striga asiatica with 34,577 predicted protein-coding genes, which reflects gene family contractions and expansions that are consistent with a three-phase model of parasitic plant genome evolution. Striga seeds germinate in response to host-derived strigolactones (SLs) and then develop a specialized penetration structure, the haustorium, to invade the host root. A family of SL receptors has undergone a striking expansion, suggesting a molecular basis for the evolution of broad host range among Striga spp. We found that genes involved in lateral root development in non-parasitic model species are coordinately induced during haustorium development in Striga, suggesting a pathway that was partly co-opted during the evolution of the haustorium. In addition, we found evidence for horizontal transfer of host genes as well as retrotransposons, indicating gene flow to S. asiatica from hosts. Our results provide valuable insights into the evolution of parasitism and a key resource for the future development of Striga control strategies.
ESTHER : Yoshida_2019_Curr.Biol_29_3041
PubMedSearch : Yoshida_2019_Curr.Biol_29_3041
PubMedID: 31522940
Gene_locus related to this paper: straf-a0a5a7qxe3

Title : Plant Chemical Biology -
Author(s) : Kinoshita T , McCourt P , Asami T , Torii KU
Ref : Plant Cell Physiol , 59 :1483 , 2018
PubMedID: 30032233

Title : Chemical Screening for Strigolactone Receptor Antagonists Using Arabidopsis thaliana - Holbrook-Smith_2018_Methods.Mol.Biol_1795_117
Author(s) : Holbrook-Smith D , McCourt P
Ref : Methods Mol Biol , 1795 :117 , 2018
Abstract : Strigolactones are a class of terpenoid-based plant hormones that are best known for their role in the suppression of axillary branching. However, strigolactones also play a role as stimulants for the germination of parasitic plants of the genera Striga and Orobanche. This dual role for strigolactones as endogenous hormones and interspecies signaling molecules has led to significant research directed toward understanding mechanisms of strigolactone perception from both the perspective of host plants and of their parasites. Antagonists for strigolactone receptors serve as potentially important tools in both arenas. This document describes the procedures required to use phenotypic screening approaches to uncover likely strigolactone receptor antagonists.
ESTHER : Holbrook-Smith_2018_Methods.Mol.Biol_1795_117
PubMedSearch : Holbrook-Smith_2018_Methods.Mol.Biol_1795_117
PubMedID: 29846923

Title : A femtomolar-range suicide germination stimulant for the parasitic plant Striga hermonthica - Uraguchi_2018_Science_362_1301
Author(s) : Uraguchi D , Kuwata K , Hijikata Y , Yamaguchi R , Imaizumi H , Am S , Rakers C , Mori N , Akiyama K , Irle S , McCourt P , Kinoshita T , Ooi T , Tsuchiya Y
Ref : Science , 362 :1301 , 2018
Abstract : The parasitic plant Striga hermonthica has been causing devastating damage to the crop production in Africa. Because Striga requires host-generated strigolactones to germinate, the identification of selective and potent strigolactone agonists could help control these noxious weeds. We developed a selective agonist, sphynolactone-7, a hybrid molecule originated from chemical screening, that contains two functional modules derived from a synthetic scaffold and a core component of strigolactones. Cooperative action of these modules in the activation of a high-affinity strigolactone receptor ShHTL7 allows sphynolactone-7 to provoke Striga germination with potency in the femtomolar range. We demonstrate that sphynolactone-7 is effective for reducing Striga parasitism without impinging on host strigolactone-related processes.
ESTHER : Uraguchi_2018_Science_362_1301
PubMedSearch : Uraguchi_2018_Science_362_1301
PubMedID: 30545887

Title : Found in Translation: Applying Lessons from Model Systems to Strigolactone Signaling in Parasitic Plants - Lumba_2017_Trends.Biochem.Sci_42_556
Author(s) : Lumba S , Subha A , McCourt P
Ref : Trends in Biochemical Sciences , 42 :556 , 2017
Abstract : Strigolactones (SLs) are small molecules that act as endogenous hormones to regulate plant development as well as exogenous cues that help parasitic plants to infect their hosts. Given that parasitic plants are experimentally challenging systems, researchers are using two approaches to understand how they respond to host-derived SLs. The first involves extrapolating information on SLs from model genetic systems to dissect their roles in parasitic plants. The second uses chemicals to probe SL signaling directly in the parasite Striga hermonthica. These approaches indicate that parasitic plants have co-opted a family of alpha/beta hydrolases to perceive SLs. The importance of this genetic and chemical information cannot be overstated since parasitic plant infestations are major obstacles to food security in the developing world.
ESTHER : Lumba_2017_Trends.Biochem.Sci_42_556
PubMedSearch : Lumba_2017_Trends.Biochem.Sci_42_556
PubMedID: 28495334

Title : Chemical genetics and strigolactone perception - Lumba_2017_F1000Res_6_975
Author(s) : Lumba S , Bunsick M , McCourt P
Ref : F1000Res , 6 :975 , 2017
Abstract : Strigolactones (SLs) are a collection of related small molecules that act as hormones in plant growth and development. Intriguingly, SLs also act as ecological communicators between plants and mycorrhizal fungi and between host plants and a collection of parasitic plant species. In the case of mycorrhizal fungi, SLs exude into the soil from host roots to attract fungal hyphae for a beneficial interaction. In the case of parasitic plants, however, root-exuded SLs cause dormant parasitic plant seeds to germinate, thereby allowing the resulting seedling to infect the host and withdraw nutrients. Because a laboratory-friendly model does not exist for parasitic plants, researchers are currently using information gleaned from model plants like Arabidopsis in combination with the chemical probes developed through chemical genetics to understand SL perception of parasitic plants. This work first shows that understanding SL signaling is useful in developing chemical probes that perturb SL perception. Second, it indicates that the chemical space available to probe SL signaling in both model and parasitic plants is sizeable. Because these parasitic pests represent a major concern for food insecurity in the developing world, there is great need for chemical approaches to uncover novel lead compounds that perturb parasitic plant infections.
ESTHER : Lumba_2017_F1000Res_6_975
PubMedSearch : Lumba_2017_F1000Res_6_975
PubMedID: 28690842

Title : The perception of strigolactones in vascular plants - Lumba_2017_Nat.Chem.Biol_13_599
Author(s) : Lumba S , Holbrook-Smith D , McCourt P
Ref : Nat Chemical Biology , 13 :599 , 2017
Abstract : Small-molecule hormones play central roles in plant development, ranging from cellular differentiation and organ formation to developmental response instruction in changing environments. A recently discovered collection of related small molecules collectively called strigolactones are of particular interest, as these hormones also function as ecological communicators between plants and fungi and between parasitic plants and their hosts. Advances from model plant systems have begun to unravel how, as a hormone, strigolactone is perceived and transduced. In this Review, we summarize this information and examine how understanding strigolactone hormone signaling is leading to insights into parasitic plant infections. We specifically focus on how the development of chemical probes can be used in combination with model plant systems to dissect strigolactone's perception in the parasitic plant Striga hermonthica. This information is particularly relevant since Striga is considered one of the largest impediments to food security in sub-Saharan Africa.
ESTHER : Lumba_2017_Nat.Chem.Biol_13_599
PubMedSearch : Lumba_2017_Nat.Chem.Biol_13_599
PubMedID: 28514432

Title : Small-molecule antagonists of germination of the parasitic plant Striga hermonthica - Holbrook-Smith_2016_Nat.Chem.Biol_12_724
Author(s) : Holbrook-Smith D , Toh S , Tsuchiya Y , McCourt P
Ref : Nat Chemical Biology , 12 :724 , 2016
Abstract : Striga spp. (witchweed) is an obligate parasitic plant that attaches to host roots to deplete them of nutrients. In Sub-Saharan Africa, the most destructive Striga species, Striga hermonthica, parasitizes major food crops affecting two-thirds of the arable land and over 100 million people. One potential weakness in the Striga infection process is the way it senses the presence of a host crop. Striga only germinates in the presence of the plant hormone strigolactone, which exudes from a host root. Hence small molecules that perturb strigolactone signaling may be useful tools for disrupting the Striga lifecycle. Here we developed a chemical screen to suppress strigolactone signaling in the model plant Arabidopsis. One compound, soporidine, specifically inhibited a S. hermonthica strigolactone receptor and inhibited the parasite's germination. This indicates that strigolactone-based screens using Arabidopsis are useful in identifying lead compounds to combat Striga infestations.
ESTHER : Holbrook-Smith_2016_Nat.Chem.Biol_12_724
PubMedSearch : Holbrook-Smith_2016_Nat.Chem.Biol_12_724
PubMedID: 27428512

Title : PARASITIC PLANTS. Probing strigolactone receptors in Striga hermonthica with fluorescence - Tsuchiya_2015_Science_349_864
Author(s) : Tsuchiya Y , Yoshimura M , Sato Y , Kuwata K , Toh S , Holbrook-Smith D , Zhang H , McCourt P , Itami K , Kinoshita T , Hagihara S
Ref : Science , 349 :864 , 2015
Abstract : Elucidating the signaling mechanism of strigolactones has been the key to controlling the devastating problem caused by the parasitic plant Striga hermonthica. To overcome the genetic intractability that has previously interfered with identification of the strigolactone receptor, we developed a fluorescence turn-on probe, Yoshimulactone Green (YLG), which activates strigolactone signaling and illuminates signal perception by the strigolactone receptors. Here we describe how strigolactones bind to and act via ShHTLs, the diverged family of alpha/beta hydrolase-fold proteins in Striga. Live imaging using YLGs revealed that a dynamic wavelike propagation of strigolactone perception wakes up Striga seeds. We conclude that ShHTLs function as the strigolactone receptors mediating seed germination in Striga. Our findings enable access to strigolactone receptors and observation of the regulatory dynamics for strigolactone signal transduction in Striga.
ESTHER : Tsuchiya_2015_Science_349_864
PubMedSearch : Tsuchiya_2015_Science_349_864
PubMedID: 26293962
Gene_locus related to this paper: strhe-ShHTL2 , strhe-ShHTL10 , strhe-ShHTL6 , strhe-ShHTL9 , strhe-ShHTL8 , strhe-ShHTL11 , strhe-ShD14 , strhe-ShHTL4 , strhe-ShHTL1 , strhe-ShHTL7 , strhe-ShHTL3 , strhe-ShHTL5

Title : Structure-function analysis identifies highly sensitive strigolactone receptors in Striga - Toh_2015_Science_350_203
Author(s) : Toh S , Holbrook-Smith D , Stogios PJ , Onopriyenko O , Lumba S , Tsuchiya Y , Savchenko A , McCourt P
Ref : Science , 350 :203 , 2015
Abstract : Strigolactones are naturally occurring signaling molecules that affect plant development, fungi-plant interactions, and parasitic plant infestations. We characterized the function of 11 strigolactone receptors from the parasitic plant Striga hermonthica using chemical and structural biology. We found a clade of polyspecific receptors, including one that is sensitive to picomolar concentrations of strigolactone. A crystal structure of a highly sensitive strigolactone receptor from Striga revealed a larger binding pocket than that of the Arabidopsis receptor, which could explain the increased range of strigolactone sensitivity. Thus, the sensitivity of Striga to strigolactones from host plants is driven by receptor sensitivity. By expressing strigolactone receptors in Arabidopsis, we developed a bioassay that can be used to identify chemicals and crops with altered strigolactone levels.
ESTHER : Toh_2015_Science_350_203
PubMedSearch : Toh_2015_Science_350_203
PubMedID: 26450211
Gene_locus related to this paper: strhe-ShHTL2 , strhe-ShHTL10 , strhe-ShHTL6 , strhe-ShHTL9 , strhe-ShHTL8 , strhe-ShHTL11 , strhe-ShHTL4 , strhe-ShHTL1 , strhe-ShHTL7 , strhe-ShHTL3 , strhe-ShHTL5

Title : Detection of Parasitic Plant Suicide Germination Compounds Using a High-Throughput Arabidopsis HTL\/KAI2 Strigolactone Perception System - Toh_2014_Chem.Biol_21_988
Author(s) : Toh S , Holbrook-Smith D , Stokes ME , Tsuchiya Y , McCourt P
Ref : Chemical Biology , 21 :988 , 2014
Abstract : Strigolactones are terpenoid-based plant hormones that act as communication signals within a plant, between plants and fungi, and between parasitic plants and their hosts. Here we show that an active enantiomer form of the strigolactone GR24, the germination stimulant karrikin, and a number of structurally related small molecules called cotylimides all bind the HTL/KAI2 alpha/beta hydrolase in Arabidopsis. Strigolactones and cotylimides also promoted an interaction between HTL/KAI2 and the F-box protein MAX2 in yeast. Identification of this chemically dependent protein-protein interaction prompted the development of a yeast-based, high-throughput chemical screen for potential strigolactone mimics. Of the 40 lead compounds identified, three were found to have in planta strigolactone activity using Arabidopsis-based assays. More importantly, these three compounds were all found to stimulate suicide germination of the obligate parasitic plant Striga hermonthica. These results suggest that screening strategies involving yeast/Arabidopsis models may be useful in combating parasitic plant infestations.
ESTHER : Toh_2014_Chem.Biol_21_988
PubMedSearch : Toh_2014_Chem.Biol_21_988
PubMedID: 25126711

Title : Thermoinhibition uncovers a role for strigolactones in Arabidopsis seed germination - Toh_2012_Plant.Cell.Physiol_53_107
Author(s) : Toh S , Kamiya Y , Kawakami N , Nambara E , McCourt P , Tsuchiya Y
Ref : Plant Cell Physiol , 53 :107 , 2012
Abstract : Strigolactones are host factors that stimulate seed germination of parasitic plant species such as Striga and Orobanche. This hormone is also important in shoot branching architecture and photomorphogenic development. Strigolactone biosynthetic and signaling mutants in model systems, unlike parasitic plants, only show seed germination phenotypes under limited growth condition. To understand the roles of strigolactones in seed germination, it is necessary to develop a tractable experimental system using model plants such as Arabidopsis. Here, we report that thermoinhibition, which involves exposing seeds to high temperatures, uncovers a clear role for strigolactones in promoting Arabidopsis seed germination. Both strigolactone biosynthetic and signaling mutants showed increased sensitivity to seed thermoinhibition. The synthetic strigolactone GR24 rescued germination of thermoinbibited biosynthetic mutant seeds but not a signaling mutant. Hormone analysis revealed that strigolactones alleviate thermoinhibition by modulating levels of the two plant hormones, GA and ABA. We also showed that GR24 was able to counteract secondary dormancy in Arabidopsis ecotype Columbia (Col) and Cape Verde island (Cvi). Systematic hormone analysis of germinating Striga helmonthica seeds suggested a common mechanism between the parasitic and non-parasitic seeds with respect to how hormones regulate germination. Thus, our simple assay system using Arabidopsis thermoinhibition allows comparisons to determine similarities and differences between parasitic plants and model experimental systems for the use of strigolactones.
ESTHER : Toh_2012_Plant.Cell.Physiol_53_107
PubMedSearch : Toh_2012_Plant.Cell.Physiol_53_107
PubMedID: 22173099

Title : A small-molecule screen identifies new functions for the plant hormone strigolactone - Tsuchiya_2010_Nat.Chem.Biol_6_741
Author(s) : Tsuchiya Y , Vidaurre D , Toh S , Hanada A , Nambara E , Kamiya Y , Yamaguchi S , McCourt P
Ref : Nat Chemical Biology , 6 :741 , 2010
Abstract : Parasitic weeds of the genera Striga and Orobanche are considered the most damaging agricultural agents in the developing world. An essential step in parasitic seed germination is sensing a group of structurally related compounds called strigolactones that are released by host plants. Although this makes strigolactone synthesis and action a major target of biotechnology, little fundamental information is known about this hormone. Chemical genetic screening using Arabidopsis thaliana as a platform identified a collection of related small molecules, cotylimides, which perturb strigolactone accumulation. Suppressor screens against select cotylimides identified light-signaling genes as positive regulators of strigolactone levels. Molecular analysis showed strigolactones regulate the nuclear localization of the COP1 ubiquitin ligase, which in part determines the levels of light regulators such as HY5. This information not only uncovers new functions for strigolactones but was also used to identify rice cultivars with reduced capacity to germinate parasitic seed.
ESTHER : Tsuchiya_2010_Nat.Chem.Biol_6_741
PubMedSearch : Tsuchiya_2010_Nat.Chem.Biol_6_741
PubMedID: 20818397