Arabidopsis NLR Immune Receptors: Structural Diversification, Signaling Networks, and Emerging Principles of Immune Activation

Plant intracellular nucleotide-binding leucine-rich repeat receptors (NLRs) are central to effector-triggered immunity (ETI), but the rapid expansion of structural data has outpaced an integrated explanation of how receptor architecture, oligomerization, and network context determine immune output. Recent structural and biochemical studies, particularly in Arabidopsis, have revealed that NLRs operate as dynamic signaling assemblies rather than simple pathogen-recognition switches. Here, we synthesize recent evidence across coiled-coil NLRs (CNLs), Toll/interleukin-1 receptor NLRs (TNLs), and RPW8-like helper NLRs (RNLs), with emphasis on mechanisms that are broadly conserved and those that remain receptor- or pathway-specific. ZAR1 (HopZ-Activated Resistance1) and selected helper RNLs form membrane-associated Ca2+-permeable channels, whereas TNLs use Toll/interleukin-1 receptor (TIR)-domain enzymatic activity to generate signaling molecules that are decoded through branch-specific modules formed by ENHANCED DISEASE SUSCEPTIBILITY1 (EDS1)–PHYTOALEXIN DEFICIENT4 (PAD4)–ACTIVATED DISEASE RESISTANCE1 (ADR1) or EDS1–SENESCENCE-ASSOCIATED GENE101 (SAG101)–N REQUIREMENT GENE1 (NRG1). Paired NLRs partition recognition and signaling, while recent work on ADR1-L1 indicates that higher-order spatial organization can further tune immune execution. We also distinguish structurally resolved complexes from inferred higher-order assemblies, examine crosstalk with cell-surface immunity and transcriptional regulation, and assess NLR-engineering strategies according to their experimental validation and potential fitness costs. Together, the evidence supports a modular view in which oligomerization is a recurrent activation principle, but biochemical output, partner dependence, and membrane execution are not interchangeable across NLR classes.