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模式识别受体FLS2的逆向工程揭示了针对逃避flg22表位的更广泛识别谱的关键设计原则。

Reverse engineering of the pattern recognition receptor FLS2 reveals key design principles of broader recognition spectra against evading flg22 epitopes.

作者信息

Zhang Songyuan, Liu Songyuan, Lai Hung-Fei, Bender Kyle W, Kim Gijeong, Caflisch Amedeo, Zipfel Cyril

机构信息

Institute of Plant and Microbial Biology, Zurich-Basel Plant Science Center, University of Zurich, Zurich, Switzerland.

Department of Biochemistry, University of Zurich, Zurich, Switzerland.

出版信息

Nat Plants. 2025 Jul 28. doi: 10.1038/s41477-025-02050-5.

DOI:10.1038/s41477-025-02050-5
PMID:40721668
Abstract

In the ongoing plant-pathogen arms race, plants use pattern recognition receptors (PRRs) to recognize pathogen-associated molecular patterns (PAMPs), while in successful pathogens, PAMPs can evolve to evade detection. Engineering PRRs to recognize evading PAMPs could potentially generate broad-spectrum and durable disease resistance. Here we reverse-engineered two natural variants of the PRR FLAGELLIN SENSING 2 (FLS2), VrFLS2XL and GmFLS2b, with extended recognition specificities towards evading flg22 variants. We identified minimal gain-of-function residues enabling blind FLS2s to recognize otherwise evading flg22 variants. We uncovered two strategies: (1) optimizing FLS2-flg22 interaction around flg22's key evasion sites and (2) strengthening direct FLS2-BAK1 interaction to overcome weak agonistic and antagonistic flg22s, respectively. In addition, we leveraged polymorphisms that enhance recognition through unknown mechanisms to engineer a superior recognition capability. These findings offer basic design principles to engineer PRRs with broader recognition spectra, paving the way for PRR engineering to generate precisely gene-edited disease-resistant crops.

摘要

在持续的植物 - 病原体军备竞赛中,植物利用模式识别受体(PRR)来识别病原体相关分子模式(PAMP),而在成功的病原体中,PAMP可以进化以逃避检测。对PRR进行工程改造以识别逃避的PAMP可能会产生广谱且持久的抗病性。在这里,我们对PRR鞭毛蛋白感应2(FLS2)的两个天然变体VrFLS2XL和GmFLS2b进行了逆向工程,使其对逃避的flg22变体具有扩展的识别特异性。我们确定了使无识别能力的FLS2能够识别原本逃避的flg22变体的最小功能获得性残基。我们发现了两种策略:(1)在flg22的关键逃避位点周围优化FLS2 - flg22相互作用,以及(2)分别加强直接的FLS2 - BAK1相互作用以克服弱激动性和拮抗性flg22变体。此外,我们利用通过未知机制增强识别的多态性来设计卓越的识别能力。这些发现为设计具有更广泛识别谱的PRR提供了基本设计原则,为通过PRR工程培育精确基因编辑的抗病作物铺平了道路。

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本文引用的文献

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Nat Plants. 2025 Jul 28. doi: 10.1038/s41477-025-02049-y.
2
Leveraging coevolutionary insights and AI-based structural modeling to unravel receptor-peptide ligand-binding mechanisms.利用共进化见解和基于人工智能的结构建模来揭示受体-肽配体结合机制。
Proc Natl Acad Sci U S A. 2024 Aug 13;121(33):e2400862121. doi: 10.1073/pnas.2400862121. Epub 2024 Aug 6.
3
Allosteric activation of the co-receptor BAK1 by the EFR receptor kinase initiates immune signaling.
EFR 受体激酶对共受体 BAK1 的别构激活启动免疫信号转导。
Elife. 2024 Jul 19;12:RP92110. doi: 10.7554/eLife.92110.
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Accurate structure prediction of biomolecular interactions with AlphaFold 3.利用 AlphaFold 3 进行生物分子相互作用的精确结构预测。
Nature. 2024 Jun;630(8016):493-500. doi: 10.1038/s41586-024-07487-w. Epub 2024 May 8.
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Targeted genome-modification tools and their advanced applications in crop breeding.靶向基因组修饰工具及其在作物育种中的应用进展。
Nat Rev Genet. 2024 Sep;25(9):603-622. doi: 10.1038/s41576-024-00720-2. Epub 2024 Apr 24.
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Editing VvDXS1 for the creation of muscat flavour in Vitis vinifera cv. Scarlet Royal.编辑 VvDXS1 以创造红皇家葡萄品种的麝香风味。
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Precision genome editing of crops for improved disease resistance.作物精准基因组编辑以提高抗病性。
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Evolutionary gain and loss of a plant pattern-recognition receptor for HAMP recognition.植物模式识别受体进化获得和丧失对 HAMP 识别的功能。
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