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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:
; ; ; ; ; ; ; ; ; ; ; ; ;  [1];  [2];  [2]
  1. (NU Sinapore)
  2. (
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
USDOE
OSTI Identifier:
1002747
Resource Type:
Journal Article
Resource Relation:
Journal Name: Nat. Struct. Mol. Biol.; Journal Volume: 17; Journal Issue: (9) ; 09, 2010
Country of Publication:
United States
Language:
ENGLISH
Subject:
36 MATERIALS SCIENCE; ABSCISIC ACID; CRYSTAL STRUCTURE; DESIGN; GERMINATION; MUTATIONS; PHOSPHATASES; PROTEINS; SEEDS

Citation Formats

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, Xu, H. Eric, Van Andel), and UCR). Identification and mechanism of ABA receptor antagonism. United States: N. p., 2010. Web. doi:10.1038/nsmb.1887.
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, Xu, H. Eric, Van Andel), & UCR). Identification and mechanism of ABA receptor antagonism. United States. doi:10.1038/nsmb.1887.
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, Xu, H. Eric, Van Andel), and UCR). Thu . "Identification and mechanism of ABA receptor antagonism". United States. doi:10.1038/nsmb.1887.
@article{osti_1002747,
title = {Identification and mechanism of ABA receptor antagonism},
author = {Melcher, Karsten and Xu, Yong and Ng, Ley-Moy and Zhou, X. Edward and Soon, Fen-Fen and Chinnusamy, Viswanathan and Suino-Powell, Kelly M and Kovach, Amanda and Tham, Fook S. and Cutler, Sean R. and Li, Jun and Yong, Eu-Leong and Zhu, Jian-Kang and Xu, H. Eric and Van Andel) and UCR)},
abstractNote = {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.},
doi = {10.1038/nsmb.1887},
journal = {Nat. Struct. Mol. Biol.},
number = (9) ; 09, 2010,
volume = 17,
place = {United States},
year = {Thu Nov 11 00:00:00 EST 2010},
month = {Thu Nov 11 00:00:00 EST 2010}
}
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