title: Identification and mechanism of ABA receptor antagonism.
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.
authors: Laboratory of Structural Sciences, Van Andel Research Institute, Grand Rapids, Michigan, USA. Karsten.Melcher@vai.org
authors: Karsten
authors: K
authors: Melcher
authors: Yong
authors: Y
authors: Xu
authors: Ley-Moy
authors: LM
authors: Ng
authors: X Edward
authors: XE
authors: Zhou
authors: Fen-Fen
authors: FF
authors: Soon
authors: Viswanathan
authors: V
authors: Chinnusamy
authors: Kelly M
authors: KM
authors: Suino-Powell
authors: Amanda
authors: A
authors: Kovach
authors: Fook S
authors: FS
authors: Tham
authors: Sean R
authors: SR
authors: Cutler
authors: Jun
authors: J
authors: Li
authors: Eu-Leong
authors: EL
authors: Yong
authors: Jian-Kang
authors: JK
authors: Zhu
authors: H Eric
authors: HE
authors: Xu
mesh_terms: D000040:Abscisic Acid / Q000378:metabolism; D017360:Arabidopsis / Q000737:chemistry* / Q000378:metabolism; D029681:Arabidopsis Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry*; D018360:Crystallography, X-Ray; D026901:Membrane Transport Proteins / Q000737:chemistry*; D008958:Models, Molecular; D009281:Naphthalenes / Q000737:chemistry*; D054730:Protein Interaction Domains and Motifs; D020836:Protein Structure, Quaternary; D013449:Sulfonamides / Q000737:chemistry*
chemical_list: D029681:Arabidopsis Proteins; D026901:Membrane Transport Proteins; D009281:Naphthalenes; C540976:AT4G17870 protein, Arabidopsis; D013449:Sulfonamides; C540973:pyrabactin; D000040:Abscisic Acid