Partial desensitization of MYC2 transcription factor alters the interaction with jasmonate signaling components and affects specialized metabolism

Xin Hou, Sanjay Kumar Singh, Joshua R. Werkman, Yongliang Liu, Qinghua Yuan, Xia Wu, Barunava Patra, Xueyi Sui, Ruiqing Lyu, Bingwu Wang, Xiaoyu Liu, Yongqing Li, Wei Ma, Sitakanta Pattanaik, Ling Yuan

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1 Scopus citations


The activity of bHLH transcription factor MYC2, a key regulator in jasmonate signaling and plant specialized metabolism, is sensitive to repression by JASMONATE-ZIM-domain (JAZ) proteins and co-activation by the mediator subunit MED25. The substitution of a conserved aspartic acid (D) to asparagine (N) in the JAZ-interacting domain (JID) of Arabidopsis MYC2 affects interaction with JAZ, although the mechanism remained unclear. The effects of the conserved residue MYC2D128 on interaction with MED25 have not been investigated. Using tobacco as a model, we generated all possible substitutions of aspartic acid 128 (D128) in NtMYC2a. NtMYC2aD128N partially desensitized the repression by JAZ proteins, while strongly interacting with MED25, resulting in increased expression of nicotine pathway genes and nicotine accumulation in tobacco hairy roots overexpressing NtMYC2aD128N compared to those overexpressing NtMYC2a. The proline substitution, NtMYC2aD128P, negatively affected transactivation and abolished the interaction with JAZ proteins and MED25. Structural modeling and simulation suggest that the overall stability of the JID binding pocket is a predominant cause for the observed effects of substitutions at D128. The D128N substitution has an overall stabilizing effect on the binding pocket, which is destabilized by D128P. Our study offers an innovative tool to increase the production of plant natural products.

Original languageEnglish
Article number126472
JournalInternational Journal of Biological Macromolecules
Early online dateAug 23 2023
StatePublished - Dec 1 2023

Bibliographical note

Funding Information:
This work is supported partially by the Harold R. Burton Endowed Professorship to L.Y., and by the grants 2018530000241001 and 2022530000241012 from the Yunnan Tobacco Company , the National Key Research and Development Program of China ( 2019YFC1711100 ), the Kentucky Tobacco Research and Development Center (KTRDC) , The Shandong Province Modern Agricultural Technology System ( SDAIT-25-02 ), The China Tobacco Shandong Industrial Corporation Major Project ( 202102004 ), The Shandong Tobacco Company Science and Technology Project ( KN294 , KN291 , KN293 , KN287 ), The Shandong Weifang Tobacco Company Science and Technology Project ( 2021-57 ), and The Shandong Rizhao Tobacco Company Science and Technology Project ( 2022-003 ). We would like to thank Huihua Ji for assistance in measuring nicotine contents in the hairy roots.

Publisher Copyright:
© 2023 The Author(s)


  • Homology structural modeling
  • MYC2
  • Protein-protein interaction
  • Specialized metabolism
  • Transcriptional regulation

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology


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