Identification and mechanism of ABA receptor antagonism

Handle URI:
http://hdl.handle.net/10754/325369
Title:
Identification and mechanism of ABA receptor antagonism
Authors:
Melcher, Karsten; Xu, Yong; Ng, Ley-Moy; Zhou, X. Edward; Soon, Fen-Fen; Chinnusamy, Viswanathan; Suino-Powell, Kelly M.; Kovach, Amanda; Tham, Fook S.; Cutler, Sean R.; Li, Jun; Yong, Eu-Leong; Zhu, Jian-Kang ( 0000-0001-5134-731X ) ; Xu, H. Eric
Abstract:
The phytohormone abscisic acid (ABA) functions through a family of fourteen PYR/PYL receptors, which were identified by resistance to pyrabactin, a synthetic inhibitor of seed germination. ABA activates these receptors to inhibit type 2C protein phosphatases, such as ABI1, yet it remains unclear whether these receptors can be antagonized. Here we demonstrate that pyrabactin is an agonist of PYR1 and PYL1 but is unexpectedly an antagonist of PYL2. Crystal structures of the PYL2-pyrabactin and PYL1-pyrabactin-ABI1 complexes reveal the mechanism responsible for receptor-selective activation and inhibition, which enables us to design mutations that convert PYL1 to a pyrabactin-inhibited receptor and PYL2 to a pyrabactin-activated receptor and to identify new pyrabactin-based ABA receptor agonists. Together, our results establish a new concept of ABA receptor antagonism, illustrate its underlying mechanisms and provide a rational framework for discovering novel ABA receptor ligands. © 2010 Nature America, Inc. All rights reserved.
KAUST Department:
Plant Stress Genomics Research Lab
Citation:
Melcher K, Xu Y, Ng L-M, Zhou XE, Soon F-F, et al. (2010) Identification and mechanism of ABA receptor antagonism. Nature Structural & Molecular Biology 17: 1102-1108. doi:10.1038/nsmb.1887.
Publisher:
Nature Publishing Group
Journal:
Nature Structural and Molecular Biology
Issue Date:
22-Aug-2010
DOI:
10.1038/nsmb.1887
PubMed ID:
20729862
PubMed Central ID:
PMC2933329
Type:
Article
ISSN:
15459993
Appears in Collections:
Articles

Full metadata record

DC FieldValue Language
dc.contributor.authorMelcher, Karstenen
dc.contributor.authorXu, Yongen
dc.contributor.authorNg, Ley-Moyen
dc.contributor.authorZhou, X. Edwarden
dc.contributor.authorSoon, Fen-Fenen
dc.contributor.authorChinnusamy, Viswanathanen
dc.contributor.authorSuino-Powell, Kelly M.en
dc.contributor.authorKovach, Amandaen
dc.contributor.authorTham, Fook S.en
dc.contributor.authorCutler, Sean R.en
dc.contributor.authorLi, Junen
dc.contributor.authorYong, Eu-Leongen
dc.contributor.authorZhu, Jian-Kangen
dc.contributor.authorXu, H. Ericen
dc.date.accessioned2014-08-27T09:49:29Zen
dc.date.available2014-08-27T09:49:29Zen
dc.date.issued2010-08-22en
dc.identifier.citationMelcher K, Xu Y, Ng L-M, Zhou XE, Soon F-F, et al. (2010) Identification and mechanism of ABA receptor antagonism. Nature Structural & Molecular Biology 17: 1102-1108. doi:10.1038/nsmb.1887.en
dc.identifier.issn15459993en
dc.identifier.pmid20729862en
dc.identifier.doi10.1038/nsmb.1887en
dc.identifier.urihttp://hdl.handle.net/10754/325369en
dc.description.abstractThe phytohormone abscisic acid (ABA) functions through a family of fourteen PYR/PYL receptors, which were identified by resistance to pyrabactin, a synthetic inhibitor of seed germination. ABA activates these receptors to inhibit type 2C protein phosphatases, such as ABI1, yet it remains unclear whether these receptors can be antagonized. Here we demonstrate that pyrabactin is an agonist of PYR1 and PYL1 but is unexpectedly an antagonist of PYL2. Crystal structures of the PYL2-pyrabactin and PYL1-pyrabactin-ABI1 complexes reveal the mechanism responsible for receptor-selective activation and inhibition, which enables us to design mutations that convert PYL1 to a pyrabactin-inhibited receptor and PYL2 to a pyrabactin-activated receptor and to identify new pyrabactin-based ABA receptor agonists. Together, our results establish a new concept of ABA receptor antagonism, illustrate its underlying mechanisms and provide a rational framework for discovering novel ABA receptor ligands. © 2010 Nature America, Inc. All rights reserved.en
dc.language.isoenen
dc.publisherNature Publishing Groupen
dc.rightsUsers may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#termsen
dc.rightsArchived with thanks to Nature Structural and Molecular Biologyen
dc.subjectabscisic aciden
dc.subjectgrowth inhibitoren
dc.subjectprotein pyl1en
dc.subjectprotein pyl2en
dc.subjectprotein pyr1en
dc.subjectpyrabactinen
dc.subjectreceptor proteinen
dc.subjectunclassified drugen
dc.subjectcomplex formationen
dc.subjectcrystal structureen
dc.subjectAbscisic Aciden
dc.subjectArabidopsisen
dc.subjectArabidopsis Proteinsen
dc.subjectCrystallography, X-Rayen
dc.subjectMembrane Transport Proteinsen
dc.subjectModels, Molecularen
dc.subjectNaphthalenesen
dc.subjectProtein Interaction Domains and Motifsen
dc.subjectProtein Structure, Quaternaryen
dc.subjectSulfonamidesen
dc.titleIdentification and mechanism of ABA receptor antagonismen
dc.typeArticleen
dc.contributor.departmentPlant Stress Genomics Research Laben
dc.identifier.journalNature Structural and Molecular Biologyen
dc.identifier.pmcidPMC2933329en
dc.eprint.versionPost-printen
dc.contributor.institutionLaboratory of Structural Sciences, Van Andel Research Institute, Grand Rapids, MI, United Statesen
dc.contributor.institutionDepartment of Obstetrics and Gynecology, National University Hospital, National University of Singapore, Singapore, Singaporeen
dc.contributor.institutionDepartment of Botany and Plant Sciences, University of California at Riverside, Riverside, CA, United Statesen
dc.contributor.institutionDepartment of Chemistry, University of California at Riverside, Riverside, CA, United Statesen
dc.contributor.affiliationKing Abdullah University of Science and Technology (KAUST)en
kaust.authorChinnusamy, Viswanathanen
kaust.authorZhu, Jian-Kangen

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