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Overall, we found this manuscript well written and appreciated the design and the robust experimental approach and the clarity of most figures. Below are specific comments that we hope will help improve the final version.

Abstract

• It would be helpful to clearly define “NLP” in the abstract as well as in the Figure 1 legend, since all other abbreviations are expanded there. Additionally, it would be better to be consistent with the writing style for full forms and abbreviationst throughout the manuscript. For example, full form could be written first followed by abbreviations.

Introduction

• The introduction would benefit from including examples of other peptide–receptor or effector-receptor complexes to provide additional context for readers less familiar with this system.

Figure 1

• Figure 1 is well presented, clearly explained, and the experiments strongly support the stated conclusions.

Figure 2

• Panel b: A sequence logo plot would visualize motif conservation more effectively. Important residues could be highlighted directly on the logo to guide interpretation.

• Panel g: It would be helpful to label Bremia directly in the figure (not only in the legend) for clarity.

Figure 3

• We appreciate the robustness of the experimental design and validation in this figure. The workflow is particularly convincing.

Figure 4

• To improve the AF3 modeling, the authors could consider incorporating an orthologous lettuce BAK1 coreceptor during complex prediction.

• Because AF3 structural predictions can vary between runs, modeling the complexes in multiple replicates using different random seeds would illustrate the consistency of confidence scores in the presented structures.

• Please include the PAE plots and the residue–residue confidence matrices for all AF3 models shown in this figure as well as in Figures S14 and S20. Given the low ipTM scores, it is currently difficult to assess the reliability of the predicted interfaces—particularly for the truncated nlp1–22 variant, where the interface appears to be flipped from original full length nlp24 model, and makes it inconclusive without replicate models and PAE support.

• Panel f: Please annotate the residue numbers on the receptor as well to help readers follow the structural description.

• Panel h: The Ponceau staining for the mutant and WT receptors appears inconsistent with earlier figures. Clarification here (and in Supplementary Fig. 13b) would be appreciated.

• In addition to the strong loss-of-function analyses, introducing a complementary reciprocal point mutation in the peptide (e.g., matching the Y522E receptor mutation) would greatly strengthen the conclusion about the functional importance of this residue pair.

Figure 5

• Panel b: Please clarify how the phylogenetic tree was generated (e.g., sequence source, alignment method, model selection, and rooting strategy).

• Panel b: The rooting and overall topology appear inconsistent with Fig. S17 and S18. A brief clarification or justification would help.

• Panel c: Including a scale bar or approximate numerical reference for the circular tracks (particularly circles 2 and 3) would improve interpretability.

Competing interests

The authors declare that they have no competing interests.

Use of Artificial Intelligence (AI)

The authors declare that they did not use generative AI to come up with new ideas for their review.