Ligand Recognition and Immune Activation by Plant NLR Receptor Pairs

- Abstract of the project

The goal of the RePairs project is to generate in depth molecular and functional knowledge on plant immune receptors from the class of nucleotide-binding (NB) and leucine-rich repeat domain (LRR) proteins (NLRs). NLRs form a large family of intracellular receptors found in both plants and animals where they are involved in pathogen perception and immune responses 1. In plants, they are the most important class of disease resistance proteins that render crops resistant against infection by major pathogens 2. Plant NLRs are subdivided into CNL, TNL or RNL clades, according to their N-terminal signaling domain that can be, respectively, a coiled-coil (CC), a TIR (Toll-Interleukin1 receptor- Resistance protein) or a RPW8 (Resistance to Powdery Mildew 8) domain. NLRs act as intracellular receptors that detect virulence factors (also called effector proteins) that pathogens secrete during infection to promote disease 3. This detection can occur in a direct manner, through physical effector- NLR interactions, or indirectly, by the recognition of effector-mediated modifications of plant proteins. Once activated, NLRs initiate rapid and potent defense reactions named the hypersensitive response (HR) that induce localized host cell death and prevent the spread of infection. The RePairs project will focus on heterologous NLR pairs consisting of one sensor NLR (sNLR) that detects the pathogen, and one executor NLR (eNLR) that initiates immune signalling. These paired NLRs provide outstanding perspectives for the engineering of resistance proteins with novel specificities 3,4. In addition to the canonical NB and LRR domains, sNLRs carry very diverse unconventional domains named integrated domains (IDs). IDs act as mimics of effector targets and play a crucial role in effector recognition, either by directly binding effectors, or by being modified post-translationally by them. This results ultimately in the immune activation the matching eNLR. Despite more than 25 years of intense investigation and the crucial role of NLR-coding genes in crop improvement, the molecular features of effector recognition and immune activation by NLRs are still poorly understood 3,4. Their understanding has been particularly hampered by the lack of suitable in vitro systems and limited structural knowledge. Breakthroughs in the purification of functional fulllength NLRs from eukaryotic expression systems and in protein structure determination by cryoelectron microscopy (cryoEM) are lifting these technical barriers. In 2019, the first structure of a plant NLR (Arabidopsis thaliana ZAR1) was determined in different functional states. This study showed how this singleton NLR of the CNL type assembles upon effector recognition in a signaling competent pentameric ring called “resistosome”

- Funding

The RePairs project is supported by ANR grant (2022-2026)

- Participants

Stella Césari (Researcher)

Thomas Kroj (Principal investigator)