Substituted Phthalimide AC94377 Is a Selective Agonist of the Gibberellin Receptor GID1

Abstract

ORCID IDs: 0000-0001-9901-5293 (K.J.); 0000-0003-0774-6203 (T.A.).Gibberellin (GA) is a major plant hormone that regulates plant growth and development and is widely used as a plant growth regulator in agricultural production. There is an increasing demand for function-limited GA mimics due to the limitations on the agronomical application of GA to crops, including GA's high cost of producing and its leading to the crops' lodging. AC94377, a substituted phthalimide, is a chemical that mimics the growth-regulating activity of GAs in various plants, despite its structural difference. Although AC94377 is widely studied in many weeds and crops, its mode of action as a GA mimic is largely unknown. In this study, we confirmed that AC94377 displays GA-like activities in Arabidopsis (Arabidopsis thaliana) and demonstrated that AC94377 binds to the Arabidopsis GIBBERELLIN INSENSITIVE DWARF1 (GID1) receptor (AtGID1), forms the AtGID1-AC94377-DELLA complex, and induces the degradation of DELLA protein. Our results also indicated that AC94377 is selective for a specific subtype among three AtGID1s and that the selectivity of AC94377 is attributable to a single residue at the entrance to the hydrophobic pocket of GID1. We conclude that AC94377 is a GID1 agonist with selectivity for a specific subtype of GID1, which could be further developed and used as a function-limited regulator of plant growth in both basic study and agriculture.

Structural basis for the regulation of phytohormone receptors

“…This accumulated evidence has resulted in the development of agonists and antagonists targeting phytohormone receptors. 96,[119][120][121] In the example of ABA receptors, ABA analogs have been designed as antagonists of ABA co-receptor interactions based on their structure. 122) The structures of some redundant ABA receptors complexed with pyrabactin also demonstrated the structural basis of why the synthetic chemical activates only a subset of the receptors, such as PYR1 and PYL1, leading to the development of quinabactin, which activates a broader range of ABA receptors than pyrabactin to effectively promote drought resistance in plants as ABA does.…”

“…This selectivity is attributed to a single residue at the GA-binding pocket of AtGID1s (AtGID1a V319 and ATGID1c I317). 96) These findings suggest a complicated manner of the growth and development through the interaction between GID1 and DELLA in Arabidopsis. Similar receptor diversity has been reported on three JA receptor COI1 in rice (OsCOI1a, OsCOI1b, and OsCOI2) although Arabidopsis genome has a single copy of COI1 gene.…”

Seed germination promoting chemical compounds and their potential use in the malting industry

“…Being a highly promising seed germination regulator, the mode of AC-94377 functioning was deeply analyzed. Despite the structural differences between GA3 and AC-94377, Jiang et al (2017) demonstrated that AC-94377 binds to the At-GID 1, an Arabidopsis GA receptor. Table 1 The list of compounds promoting seed germination of barley and other plant species.…”

Helminthosporic acid functions as an agonist for gibberellin receptor

“…The primers for PCR, AtGA3ox1, AtEXP1 (encoding expansin1) and AtACT7 (encoding actin7) were used as described previously. 20) OsGA20ox2, OsGA2ox4 (Os05g0514600), and the housekeeping gene OsACT1 (encoding actin1) were amplified with the following primers: OsGA20ox2-forward (5′-GCCAATGGGGAGGG TGT-3′) and -reverse (5′-CCATGATCGTCAGCGACA-3′), OsGA2ox4-forward (5′-AGGAGCTTGCTTCCAAC AAAG-3′) and -reverse (5′-CAACAGGTTTCCCAA-CACTG-3′), and OsACT1-forward (5′-TGGCATCTCT-CAGCACATTCC-3′) and -reverse (5′-TGTGCACAAT GGATGGG-3′).…”

“…Docking simulation analysis of interactions between H-acid and OsGID1 was performed with Chimera and AutoDock Vina based on the data for 3EBL from the Protein Data Bank as described previously. 20) Results GA-like activity of H-acid in rice and Arabidopsis GA-like activities of H-acid have been demonstrated in many plants such as rice, grass, and tobacco. [10][11][12]…”