Structural basis of NPR1 in activating plant immunity

Nature. 2022 May;605(7910):561-566. doi: 10.1038/s41586-022-04699-w. Epub 2022 May 11.


NPR1 is a master regulator of the defence transcriptome induced by the plant immune signal salicylic acid1-4. Despite the important role of NPR1 in plant immunity5-7, understanding of its regulatory mechanisms has been hindered by a lack of structural information. Here we report cryo-electron microscopy and crystal structures of Arabidopsis NPR1 and its complex with the transcription factor TGA3. Cryo-electron microscopy analysis reveals that NPR1 is a bird-shaped homodimer comprising a central Broad-complex, Tramtrack and Bric-à-brac (BTB) domain, a BTB and carboxyterminal Kelch helix bundle, four ankyrin repeats and a disordered salicylic-acid-binding domain. Crystal structure analysis reveals a unique zinc-finger motif in BTB for interacting with ankyrin repeats and mediating NPR1 oligomerization. We found that, after stimulation, salicylic-acid-induced folding and docking of the salicylic-acid-binding domain onto ankyrin repeats is required for the transcriptional cofactor activity of NPR1, providing a structural explanation for a direct role of salicylic acid in regulating NPR1-dependent gene expression. Moreover, our structure of the TGA32-NPR12-TGA32 complex, DNA-binding assay and genetic data show that dimeric NPR1 activates transcription by bridging two fatty-acid-bound TGA3 dimers to form an enhanceosome. The stepwise assembly of the NPR1-TGA complex suggests possible hetero-oligomeric complex formation with other transcription factors, revealing how NPR1 reprograms the defence transcriptome.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Intramural

MeSH terms

  • Arabidopsis Proteins* / metabolism
  • Arabidopsis* / metabolism
  • Basic-Leucine Zipper Transcription Factors / metabolism
  • Cryoelectron Microscopy
  • Gene Expression Profiling
  • Gene Expression Regulation, Plant
  • Plant Immunity
  • Plant Proteins / metabolism
  • Salicylic Acid / metabolism
  • Transcription Factors / metabolism


  • Arabidopsis Proteins
  • Basic-Leucine Zipper Transcription Factors
  • NPR1 protein, Arabidopsis
  • Plant Proteins
  • Transcription Factors
  • Salicylic Acid