The Plant “Resistosome”: Structural Insights into Immune Signaling

Abstract

Plant innate immunity is triggered via direct or indirect recognition of pathogen effectors by the NLR family immune receptors. Mechanistic understanding of plant NLR function has relied on structural information from individual NLR domains and inferences from studies on animal NLRs. Recent reports of the cryo-EM structures of the Arabidopsis plant immune receptor ZAR1 in monomeric inactive and transition states, as well as the active oligomeric state or the ''resistosome,'' have afforded a quantum leap in our understanding of how plant NLRs function. In this Review, we outline the recent structural findings and examine their implications for the activation of plant immune receptors more broadly. We also discuss how NLR signaling in plants, as illustrated by the ZAR1 structure, is analogous to innate immune receptor signaling mechanisms across kingdoms, drawing particular attention to the concept of signaling by cooperative assembly formation.

Inflammasomes contributing to inflammation in arthritis

“…The generic modular organization of NLR proteins is formed by a conserved tripartite domain structure consisting of a N‐terminal recruiting domain, a central nucleotide‐binding domain that is capable of oligomerization, and a C‐terminal leucine‐rich repeat (LRR) domain that regulates the assembly of the complex. This modular organization is found in several innate immune pathways in mammals and in plants where they form the largest family of defense molecules . While plant and mammalian NLRs are structurally and functionally very similar, they are believed to be the product of convergent evolutions, indicating that this successful modular architecture may underline a possible conserved strategy of cellular host defenses.…”

“…This modular organization is found in several innate immune pathways in mammals and in plants where they form the largest family of defense molecules. 8,9 While plant and mammalian NLRs are structurally and functionally very similar, they are believed to be the product of convergent evolutions, 10 indicating that this successful modular architecture may underline a possible conserved strategy of cellular host defenses.…”

Jurassic NLR: conserved and dynamic evolutionary features of the atypically ancient immune receptor ZAR1

“…Mutations of glutamic acid (E) 11 and E18 impaired Arabidopsis ZAR1-mediated cell death without interfering with oligomerization and plasma membrane association (Wang et al 2019b). The E130/E134 ring was previously discussed as potentially having Ca 2+ transporter activity because of structural similarity to rings in the structures of the mitochondrial calcium uniporter from Caenorhabditis elegans and the calcium release-activated calcium channel ORAI from Drosophila melanogaster (Burdett et al, 2019). Whereas E11 is conserved in 94% of ZAR1 orthologs, only 3–18% retain E18, E130 and E134 in the same positions as Arabidopsis ZAR1.…”

A molecular roadmap to the plant immune system

“…The released H1 helix then associates with the H1 helices of neighboring activated ZAR1 molecules, resulting in the formation of a funnel-like structure with a striking hydrophobic surface. There is evidence that the ZAR1 CC domain funnel is required for membrane association and that this membrane association is linked to induction of cell death, potentially through ion efflux or membrane perturbation ( 14 , 15 , 224 ).…”