Exploring the interaction mechanism between antagonist and the jasmonate receptor complex by molecular dynamics simulation.

Jasmonates induce the protein-protein interaction between the F-box protein CORONATINE INSENSITIVE 1 (COI1) and jasmonate ZIM-domain proteins (JAZs) in the presence of inositol phosphate, which made the degradation of JAZs and the release of the JAZ-repressed transcription factors. They are involved in the regulation of a wide range of physiology process, including plant growth, development and stress response. Coronatine-O-methyloxime (COR-MO) prevents the binding of COI1-JAZ, acting as an antagonist for jasmonate signaling pathway, while the understanding on the molecular basis of its action as an antagonist is still lacking at atomic level. In this study, we explored the interaction mechanism of jasmonate antagonists through molecular docking, molecular dynamics (MD) simulation, residue interaction network analysis and binding free energy calculation. Compared with the agonists, the conformation of JAZ1 is different in response to the binding with antagonist. Antagonists lost hydrogen bond interaction with Ala204 and Arg206 in JAZ1, and Arg496 in COI1, which results that the sidechain of Arg206 in JAZ1 rotates and unable to penetrate into COI1, so that it lost interaction with 1,5-InsP8. It is indicated that the agonist is more closely associated with 1,5-InsP8 than the antagonist based on the residue interaction network analysis. The binding free energy of JA-Ile-MO/COR-MO with JAZ1 is higher than that of JA-Ile/COR. It is unfavorable for the binding of JAZ1 with COI1 in the presence of antagonists. This study provides a basis for the understanding of the interaction mechanism of jasmonate agonists/antagonists, which will contribute to the discovery of novel jasmonate agonists/antagonists.