A conserved structural logic underlies sensor–helper communication in the NRC immune receptor network
Year: 2026
Type: article
Abstract: Plants deploy intracellular immune receptors called NLRs to detect pathogens and mount defence responses. NLRs can function as multifunctional “singletons”, or in complex pairs and networks of functionally specialized receptors. In the NRC network, "sensor" NLRs recognise pathogen effectors and activate downstream "helper" NLRs that execute immune signaling and cell death. Although sensor–helper communication is central to disease resistance in many crops, the structural basis of signal transduction in the NRC network has remained elusive, in part due to the transient nature of sensor-helper interactions. We used AlphaFold 3 to study activation in this network, using the sensor Rx and its helper NRC2a as a system. Modeling of the Rx-NRC2a complex, revealed a previously uncharacterized interface mediated by the sensor's NB and the helper's NB and LRR domains. To test whether this predicted interface is functionally relevant, we designed structure-guided point mutations in both Rx and NRC2a and characterised them using cell death assays in Nicotiana benthamiana. We identified residues on both sides of the interface that are essential for helper activation and confirmed the specificity of these contacts through reciprocal charge- swap experiments that rescued a critical salt bridge. Building on the observation that this interaction logic appears structurally conserved across NRC network-encoding species, we applied structure prediction to study sensor-helper communication in the compact NRC network of lettuce. Structure-guided swaps of the NB-domain interface regions allowed us to expand the helper compatibility profile of a lettuce sensor NLR. These results provide a structural framework for understanding and engineering sensor–helper communication, with direct implications for bioengineering disease resistance in crops.
Language: English
Subfield: Plant Science
Domain: Life Sciences
SDG: Zero hunger
Open Access status: green
OpenAlex ID: W7207766596