Inositol pyrophosphates promote the interaction of SPX domains with the coiled-coil motif of PHR transcription factors to regulate plant phosphate homeostasis

Nat Commun. 2021 Jan 15;12(1):384. doi: 10.1038/s41467-020-20681-4.


Phosphorus is an essential nutrient taken up by organisms in the form of inorganic phosphate (Pi). Eukaryotes have evolved sophisticated Pi sensing and signaling cascades, enabling them to stably maintain cellular Pi concentrations. Pi homeostasis is regulated by inositol pyrophosphate signaling molecules (PP-InsPs), which are sensed by SPX domain-containing proteins. In plants, PP-InsP-bound SPX receptors inactivate Myb coiled-coil (MYB-CC) Pi starvation response transcription factors (PHRs) by an unknown mechanism. Here we report that a InsP8-SPX complex targets the plant-unique CC domain of PHRs. Crystal structures of the CC domain reveal an unusual four-stranded anti-parallel arrangement. Interface mutations in the CC domain yield monomeric PHR1, which is no longer able to bind DNA with high affinity. Mutation of conserved basic residues located at the surface of the CC domain disrupt interaction with the SPX receptor in vitro and in planta, resulting in constitutive Pi starvation responses. Together, our findings suggest that InsP8 regulates plant Pi homeostasis by controlling the oligomeric state and hence the promoter binding capability of PHRs via their SPX receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Arabidopsis / physiology*
  • Arabidopsis Proteins / genetics
  • Arabidopsis Proteins / isolation & purification
  • Arabidopsis Proteins / metabolism*
  • Arabidopsis Proteins / ultrastructure
  • Crystallography, X-Ray
  • Diphosphates / metabolism*
  • Gene Expression Regulation, Plant*
  • Inositol Phosphates / metabolism*
  • Mutation
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Protein Binding / genetics
  • Protein Domains / genetics
  • Recombinant Proteins / genetics
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / ultrastructure
  • Signal Transduction / genetics
  • Transcription Factors / genetics
  • Transcription Factors / isolation & purification
  • Transcription Factors / metabolism*
  • Transcription Factors / ultrastructure


  • Arabidopsis Proteins
  • Diphosphates
  • Inositol Phosphates
  • Nuclear Proteins
  • PHR1 protein, Arabidopsis
  • Recombinant Proteins
  • SPX1 protein, Arabidopsis
  • Transcription Factors