TY - JOUR
T1 - Identification and mechanism of ABA receptor antagonism
AU - Melcher, Karsten
AU - Xu, Yong
AU - Ng, Ley-Moy
AU - Zhou, X. Edward
AU - Soon, Fen-Fen
AU - Chinnusamy, Viswanathan
AU - Suino-Powell, Kelly M.
AU - Kovach, Amanda
AU - Tham, Fook S.
AU - Cutler, Sean R.
AU - Li, Jun
AU - Yong, Eu-Leong
AU - Zhu, Jian-Kang
AU - Xu, H. Eric
N1 - KAUST Repository Item: Exported on 2020-10-01
PY - 2010/8/22
Y1 - 2010/8/22
N2 - 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.
AB - 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.
UR - http://hdl.handle.net/10754/325369
UR - http://www.nature.com/articles/nsmb.1887
UR - http://www.scopus.com/inward/record.url?scp=77956345169&partnerID=8YFLogxK
U2 - 10.1038/nsmb.1887
DO - 10.1038/nsmb.1887
M3 - Article
C2 - 20729862
SN - 1545-9993
VL - 17
SP - 1102
EP - 1108
JO - Nature Structural & Molecular Biology
JF - Nature Structural & Molecular Biology
IS - 9
ER -