Ligand-triggered allosteric ADP release primes a plant NLR complex

Science. 2019 Apr 5;364(6435):eaav5868. doi: 10.1126/science.aav5868.


Pathogen recognition by nucleotide-binding (NB), leucine-rich repeat (LRR) receptors (NLRs) plays roles in plant immunity. The Xanthomonas campestris pv. campestris effector AvrAC uridylylates the Arabidopsis PBL2 kinase, and the latter (PBL2UMP) acts as a ligand to activate the NLR ZAR1 precomplexed with the RKS1 pseudokinase. Here we report the cryo-electron microscopy structures of ZAR1-RKS1 and ZAR1-RKS1-PBL2UMP in an inactive and intermediate state, respectively. The ZAR1LRR domain, compared with animal NLRLRR domains, is differently positioned to sequester ZAR1 in an inactive state. Recognition of PBL2UMP is exclusively through RKS1, which interacts with ZAR1LRR PBL2UMP binding stabilizes the RKS1 activation segment, which sterically blocks ZAR1 adenosine diphosphate (ADP) binding. This engenders a more flexible NB domain without conformational changes in the other ZAR1 domains. Our study provides a structural template for understanding plant NLRs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate / chemistry*
  • Adenosine Diphosphate / metabolism
  • Arabidopsis / enzymology*
  • Arabidopsis / microbiology*
  • Arabidopsis Proteins / chemistry*
  • Arabidopsis Proteins / metabolism
  • Bacterial Proteins / metabolism
  • Carrier Proteins / chemistry*
  • Cryoelectron Microscopy
  • Intracellular Signaling Peptides and Proteins / chemistry*
  • Ligands
  • Membrane Proteins
  • NLR Proteins / chemistry*
  • Nucleoside-Phosphate Kinase / metabolism
  • Phosphoproteins / chemistry*
  • Protein Domains
  • Protein-Serine-Threonine Kinases / chemistry*
  • Protein-Serine-Threonine Kinases / metabolism
  • Xanthomonas campestris / enzymology


  • Arabidopsis Proteins
  • Bacterial Proteins
  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • Ligands
  • Membrane Proteins
  • NLR Proteins
  • PKS1 protein, Arabidopsis
  • Phosphoproteins
  • ZAR1 protein, Arabidopsis
  • Adenosine Diphosphate
  • APK2a protein, Arabidopsis
  • Protein-Serine-Threonine Kinases
  • uridine monophosphate kinase
  • Nucleoside-Phosphate Kinase