Journal Article

Ligand-triggered allosteric ADP release primes a plant NLR complex

Qi, Yijun, Gao, Ning, Wang, Guoxun, Wang, Jizong, Zhou, Jian-Min, Hu, Meijuan, Qi, Jinfeng, Han, Zhifu, Wu, Shan, Wang, Jia, Wang, Hong-Wei, Chai, Jijie

2019

Overview

Nucleotide-binding, leucine-rich repeat receptors (NLRs) initiate immune responses when they sense a pathogen-associated effector. In animals, oligomerization of NLRs upon binding their effectors is key to downstream activity, but plant systems differ in many ways and their activation mechanisms have been less clear. In two papers, Wang et al. studied the composition and structure of an NLR called ZAR1 in the small mustard plant Arabidopsis (see the Perspective by Dangl and Jones). They determined cryo–electron microscopy structures that illustrate differences between inactive and intermediate states. The active, intermediate state of ZAR1 forms a wheel-like pentamer, called the resistosome. In this activated complex, a set of helices come together to form a funnel-shaped structure required for immune responsiveness and association with the plasma membrane. Science , this issue p. eaav5868 , p. eaav5870 ; see also p. 31 Structural, biochemical, and functional studies show how a plant immune resistosome complex mediates cell death and disease resistance. 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 (PBL2 UMP ) 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-PBL2 UMP in an inactive and intermediate state, respectively. The ZAR1 LRR domain, compared with animal NLR LRR domains, is differently positioned to sequester ZAR1 in an inactive state. Recognition of PBL2 UMP is exclusively through RKS1, which interacts with ZAR1 LRR . PBL2 UMP 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.

• Publisher: American Association for the Advancement of Science,The American Association for the Advancement of Science
• Subject: Activation / Adenosine diphosphate / Adenosine Diphosphate - chemistry / Adenosine Diphosphate - metabolism / Adenosine triphosphate / Allosteric properties / Animals / Apaf-1 protein / Apoptosis / Arabidopsis - enzymology / Arabidopsis - microbiology / Arabidopsis Proteins - chemistry / Arabidopsis Proteins - metabolism / Arabidopsis thaliana / Assaying / ATP / Bacterial Proteins - metabolism / Black rot / Carrier Proteins - chemistry / Cell death / Coils / Cryoelectron Microscopy / Domains / Effectors / Electron microscopy / Helices / Hypersensitive response / Immune response / Immunity / Intracellular Signaling Peptides and Proteins - chemistry / Kinases / Leucine / Ligands / Membrane Proteins / Microscopy / Molecular machines / Mustard / NLR Proteins - chemistry / Nucleoside-Phosphate Kinase - metabolism / Oligomerization / Pathogens / Phosphoproteins - chemistry / Plant immunity / Protein Domains / Protein kinase / Protein-Serine-Threonine Kinases - chemistry / Protein-Serine-Threonine Kinases - metabolism / Proteins / Radiolabelling / Receptors / Recognition / RESEARCH ARTICLE SUMMARY / Transmission electron microscopy / Xanthomonas campestris / Xanthomonas campestris - enzymology