Assistant Project Scientist University of California, Riverside
Abscisic acid (ABA) is an essential phytohormone that helps plants adapt to several biotic and abiotic stresses. ABA binds to PYR/PYL/RCAR receptors (PYLs) and forms a complex that inhibits group-A protein phosphatases 2C (PP2Cs), negative regulators of ABA signaling. Novel scaffolds that can agonize and antagonize these receptors may help dissect the roles of ABA in various physiological processes and be useful for manipulating abiotic stress responses, transpiration, and plant growth. While there are several promising leads for ABA agonists such as Opabactin (OP), the current leads for ABA antagonists are only modestly active in Arabidopsis. To address this limitation we used a click chemistry approach to design Antabactin (ANT) an OP derived peptido-triazole which is a pan antagonist of ABA receptors with up to 1000 fold increase in PYR1 affinity relative to ABA. A PYL10-antabactin structure reveals that antabactin occupies both the 3’ and 4’-tunnels in ABA receptors, preventing binding to PP2Cs. ANT treatments promote seed germination, lower leaf temperature to mimic the ABA signaling mutant (abi1C) and abrogate ABA signaling induced by osmotic stress in Arabidopsis thaliana indicating strong bioactivity. This study provides a novel approach for the rational design antagonist of ABA receptors that can be utilized as probes to dissect ABA signaling in plants.
Coauthors: Francis Peterson – University of Wisconsin, Madison;Dezi Elzinga – University of California, Riverside;Sang-Youl Park – University of California, Riverside;Zenan Xing – University of California, Riverside;James Eckhardt – University of California, Riverside;Julianna Faria – University of California, Riverside;Sean Cutler – University of California, Riverside