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

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Abstract

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.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

This work was funded by the Natural Science Foundation of Shandong Province, China (Grant No. ZR2018QB004), the Talents of High Level Scientific Research Foundation (Grant No. 6631113318) of Qingdao Agricultural University, and the National Natural Science Foundation of China (Grant No. 81903748). We are thankful for the software provided by professor Xiaojun Yao at Lanzhou university.

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  1. Mengqi Cui and Kun Zhang have contributed equally to this work.

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  1. Shandong Province Key Laboratory of Applied Mycology, College of Life Science, Qingdao Agricultural University, Qingdao, 266109, China

    Mengqi Cui, Kun Zhang, Ruihan Wu & Juan Du

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Contributions

JD conceived and supervised the experiments. MQC, KZ, and RHW performed MD simulations. MQC, KZ, and RHW analyzed the data. MQC and JD wrote the paper.

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Correspondence to Juan Du.

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Supplementary file1 (DOCX 15 kb)

10822_2022_441_MOESM2_ESM.tif

Supplementary file2 (TIF 74 kb). Figure S1 The total number of H-bonds formed between ligand and the receptor. (A) system 1, COI1+ASK1+JAZ1+1,5-InsP8+JA-Ile-MO, (B) system 2, COI1+ASK1+JAZ1+1,5-InsP8+COR-MO, (C) system 3, COI1+ASK1+JAZ1+1,5InsP8+JA-Ile, (D) system 4, COI1+ASK1+JAZ1+1,5-InsP8+COR. (E) The occupancy of hydrogen bond formed between ligand and the receptor

10822_2022_441_MOESM3_ESM.tif

Supplementary file3 (TIF 404 kb). Figure S2 The interaction of COR-MO/COR (sphere representation) with COI1 (gray; ribbon representation), JAZ1 degron (yellow; surface representation) and 1,5-InsP8 (sphere representation). (A) system 2, COI1+ASK1+JAZ1+1,5-InsP8+COR-MO; (B) system 4, COI1+ASK1+JAZ1+1,5-InsP8+COR

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Cui, M., Zhang, K., Wu, R. et al. Exploring the interaction mechanism between antagonist and the jasmonate receptor complex by molecular dynamics simulation. J Comput Aided Mol Des 36, 141–155 (2022). https://doi.org/10.1007/s10822-022-00441-w

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