A lettuce receptor-like kinase recognizes the highly conserved heptapeptide motif within microbial NEP1-like proteins

Plants rely on cell surface immune receptors to detect microbial patterns and initiate effective defense responses. Although the Asteraceae family is one of the largest and economically important plant groups, little information is available about its pattern-triggered immunity signaling. Cultivated lettuce ( Lactuca sativa L.) recognizes a 24-amino acid peptide (nlp24) from necrosis- and ethylene-inducing peptide 1-like proteins (NLPs) found in bacteria, fungi, and oomycetes. Here, we perform an extensive characterization of nlp24-induced immune responses in lettuce and identify the LETTUCE nlp24 RECEPTOR (LNR) as the leucine-rich repeat receptor-like kinase mediating its recognition. Remarkably, nlp24 recognition in lettuce and subsequent activation of defenses strongly depend on the conserved heptapeptide motif (GHRHDWE). Structural modeling-guided mutagenesis experiments suggest that residues in the nlp24 heptapeptide interact with a hydrophobic pocket in the LNR solenoid structure. Divergent ligand specificities and the absence of sequence homology between LNR and Arabidopsis nlp24-recognizing receptor indicate that the NLP recognition in lettuce and Arabidopsis emerged independently, through convergent evolution. Our phylogenetic analysis shows that LNR is closely related to Arabidopsis MIK2 (MALE DISCOVERER 1-INTERACTING RECEPTOR-LIKE KINASE 2), but belongs to a distinct, Asteraceae-specific monophyletic subgroup that has undergone a significant expansion in Lactuca . Our findings provide insights into the mechanisms of pattern-triggered immunity in lettuce and the fast evolution of its immune receptor repertoire. On the translational side, our findings open opportunities for the crop defense improvement via interfamily transfer.