Plant NLR resistosome activation and signalling

Effector-triggered immunity by plant NB-LRR receptors. Direct or indirect recognition of a pathogen effector switches the NB-ARC domain from ADP- to ATP-bound and drives oligomerisation into a resistosome. The N-terminal signalling domain then determines the output chemistry: coiled-coil (CC) domains assemble a funnel that acts as a calcium-permeable cation channel, whereas TIR domains assemble paired active sites with NAD+-cleaving activity whose nucleotide products are received by EDS1-family heterodimers, which in turn recruit helper RNLs that are themselves calcium channels. Both branches converge on Ca2+ influx and the hypersensitive response.

Boundary. The module starts at effector recognition and ends at the Ca2+-conducting resistosome or RNL channel. Upstream PRR/PTI signalling and the downstream transcriptional and salicylate programmes are separate biology and are left out. The pathogen effectors themselves are not represented as annotons: recognition is modelled from the host side only, so e.g. the PBL2 decoy carries no function and no in-module modifier because the uridylylating effector AvrAC is outside the module. Why one module with variant sets rather than separate CNL and TNL modules. The two branches share the same backbone - LRR-mediated recognition, NB-ARC nucleotide switch, oligomerisation - and converge on the same Ca2+ output. Splitting them would duplicate parts 1 and 2 and hide the convergence, so the N-terminal domain class is modelled as the variation axis instead. Part 3 is optional because it is reached only from the TIR variant. Deliberately kept as prose, not modelled as annotons: (1) NRC networks. The helper NRCs of asterids form hexameric resistosomes and act downstream of sensor CNLs without being incorporated into the active complex. The key structures (NbNRC2 PDB 9FP6, SlNRC3 9RI9, NbNRC4 9CC8), the AVRcap1b inhibition mechanism and the inositol-phosphate cofactor come from very recent work and in several cases from preprints cited by PMID:41614442 (Guo et al. 2025, Seager et al. 2025). The activation-and-release model would also need a connection type this module cannot yet assert cleanly, since no hetero-oligomer between sensor and helper has been demonstrated. Revisit when the primary papers are published and the NRC accessions are in reviewed UniProt entries; N. benthamiana NRC2 has no reviewed accession at present. (2) Other CNL architectures. Sr35 (wheat) is a directly-recognising pentameric CNL and would fit the cnl_direct variant, but its only UniProt record is the unreviewed S5ABD6, whose protein name is "CNL9"; rather than attach a confusing label, the direct-recognition CNL case is represented here by the TNL direct variant and by this note. MLA13 forms a heterodimer with its effector with no resistosome detected, and CCG10-NLRs such as RPS2 may be octameric - both are single recent reports and neither is modelled. (3) 2'cADPR. It is a biomarker of TNL activation and a plausible precursor of pRib-AMP, but it does not itself activate the EDS1 complexes, so it is not modelled as a messenger of this pathway. (4) NRG1C. The truncated NRG1C variant inhibits ESN signalling by sequestering EDS1-SAG101. This is negative regulation of part 3 rather than a step of it. Channel activities on ZAR1, ADR1 and NRG1.1 are asserted at module level from electrophysiology, and GOA currently carries no calcium-channel annotation for any of them. Note that the primary electrophysiology describes non-selective, Ca2+-permeable cation channels ("calcium-permeable cation-selective channel activity", PMID:33984278; "Ca2+-permeable cation channels", PMID:34140391) rather than Ca2+-selective channels, so GO:0005262 calcium channel activity is used here for the biologically salient conductance, but a monoatomic cation-channel parent (GO:0005261) may be the better fit if these become gene annotations. They are recorded here as module claims with their primary evidence; whether they should become gene annotations is a question for the respective gene reviews (ARATH EDS1, PAD4, RPM1 and RPS2 reviews exist; ZAR1, ADR1, NRG1.1, RPP1 and SAG101 have no gene folder yet).