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Scientists Discover Resistosome, Illuminating Plant Disease Resistance Mechanisms
Like animals, plants possess an immune system to fight off invading parasites. Unlike vertebrate animals that possess both adaptive immunity and innate immunity, plants solely rely on innate immunity, which deploys immune receptors to detect molecules derived from parasites and activate defenses. Plant innate immune receptors are encoded by disease resistance genes and include surface-localized receptors and cytoplasmic nucleotide-binding leucine-rich receptors (NLRs), the latter also exists in animals.
Upon perception of microbial molecules, some animal NLRs are known to form oligomeric inflamasomes that recruit caspases to trigger cell death. It remains unknown, however, whether plant NLRs also form oligomers and, if so, how an oligomeric plant NLR trigger defenses. It has been 25 years since the isolation of first plant disease resistance genes, but our understanding of plant NLR proteins remain inadequate, largely because of a lack of a structure for full-length plant NLR.
In a recent study a team led by scientists at Tsinghua University (TU) and Institute of Genetics and Developmental Biology of Chinese Academy of Sciences (IGDB CAS) solved the first structures of a full-length plant NLR protein and uncovered previously unknown mechanisms of this important class of immune receptors.
The IGDB team previously found that the bacterial pathogen Xanthomonas campestris campestris deliberately secretes into plant cells a virulence protein called AvrAC, an uridylylate transferase, to subvert immune signaling downstream of cell-surface immune receptors. They later found that Arabidopsis plants employ an NLR protein called ZAR1, an adaptor protein RKS1, and a decoy protein PBL2 to accurately sense virulence activity of AvrAC. As such, PBL2, RKS1 and the cytoplasmic NLR receptor ZAR1 act together as a trap to monitor bacterial activity and trigger disease resistance.
In the current study, the joined team applied cryoEM to first solve two structures of ZAR1 protein complexes, a resting state ADP-bound ZAR1-RKS1 binary complex and a ZAR1-RKS1-PBL2UMP tertiary complex. This allowed mapping of critical structural features, including ADP-binding and intra-molecular interactions among different domains of ZAR1, required to keep an NLR at a resting state prior to pathogen perturbation.
The authors further found that the in vitro assembled ZAR1-RKS1-PBL2UMP tertiary complex exists at an intermediate/primed state, in which the binding of PBL2UMP to RKS1 triggers steric clash between an RKS1 segment and the nucleotide binding domain (NBD) of ZAR1, leading to depletion of ADP from ZAR1. The authors further showed that upon addition of ATP or dATP, the ZAR1-RKS1-PBL2UMP tertiary complex forms a pentameric structure named resistosome, demonstrating for the first time that a plant NLR also oligomerize upon activation.
CryoEM structure of resistosome and further biochemical and functional analyses demonstrated that the formation of resistosome is essential for disease resistance and hypersensitive cell death-triggering conferred by ZAR1. While the ZAR1 resistosome resemble animal inflamasomes in various ways, the study showed that the ZAR1 protein possess an N terminal α helix which acts as a “death switch” that specifically pups up in the activated resistosome to form a pore at plasma membrane. This triggers cell death and activation of disease resistance.
NLRs are the largest family of plant immune receptors, and each plant species host up to hundreds of NLRs conferring resistance to a wide range of parasites including phytopathogenc viruses, bacteria, fungi, oomycetes, nematode, insects, and parasitic weeds. The findings of this study shed light on the elucidation of disease/pest resistance mechanisms in numerous plant-parasite systems. Knowledge gained opens up new avenues for better control of disease/pest damage to crop plants. 
The study was published as two back-to-back research articles in Science on April 5, 2019. In the same issue, Profs. Jeff Dangl and Jonathan Jones wrote a perspective entitled “High five: a pentangular plant inflammasome” for the two articles commenting on the work. Dr. WANG Jizong (TU, IGDB), Dr. WANG Jia (TU), and Ms. HU Meijuan (IGDB) are co-first authors for the first paper entitled “Ligand-triggered allosteric ADP release primes a plant NLR complex”. Dr. WANG Jizong, Ms. HU Meijuan and Dr. WANG Jia were the co-first authors of the second paper entitled “Reconstitution and structure of a plant NLR resistosome conferring immunity”. Profs. CHAI Jijie (TU), Jian-Min Zhou (IGDB), and WANG Hongwei (TU) were co-corresponding authors for both papers.
The work was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB11020200) and the National Natural Science Foundation of China (31421001).
Figure 1. Diagram depicting dynamic process of ZAR1 NLR activation.Color-coded are PBL2, RKS1, and different domains of ZAR1. The binding of PBL2UMP as a ligand to RKS1 triggers the release of ADP from ZAR1, permitting incorporation of ATP/dATP. The binding of ATP triggers conformational changes in ZAR to expose surfaces necessary for oligomerization between neighboring ZAR1 proteins. The boxed structure highlights the death switch pupping out from the active resistosome. (Image by WANG et al.)
Mr. QI Lei
Institute of Genetics and Developmental Biology, Chinese Academy of Sciences