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通过合理的受体工程解锁扩展的鞭毛蛋白感知

Unlocking expanded flagellin perception through rational receptor engineering.

作者信息

Li Tianrun, Jarquin Bolaños Esteban, Stevens Danielle M, Sha Hanxu, Prigozhin Daniil M, Coaker Gitta

机构信息

Department of Plant Pathology, University of California Davis, Davis, CA, USA.

Plant and Microbial Biology, University of California Berkeley, Berkeley, CA, USA.

出版信息

Nat Plants. 2025 Jul 28. doi: 10.1038/s41477-025-02049-y.

DOI:10.1038/s41477-025-02049-y
PMID:40721669
Abstract

The surface-localized receptor kinase FLS2 detects the flg22 epitope from bacterial flagella. FLS2 is conserved across land plants, but bacterial pathogens exhibit polymorphic flg22 epitopes. Most FLS2 homologues possess narrow perception ranges, but four with expanded perception have been identified. Using diversity analyses, AlphaFold modelling and amino acid properties, key residues enabling expanded recognition were mapped to FLS2's concave surface, interacting with the co-receptor and polymorphic flg22 residues. Synthetic biology enabled engineering of expanded recognition from QvFLS2 (Quercus variabilis) into a homologue with canonical perception. A similar approach enabled transfer of Agrobacterium perception from FLS2 (Vitis riparia) into VrFLS2. Evolutionary analyses across three plant orders showed residues under positive selection aligning with those binding the co-receptor and flg22's C terminus, suggesting more alleles with expanded perception exist. Our experimental data enabled the identification of specific receptor amino acid properties and AlphaFold3 metrics that facilitate predicting FLS2-flg22 recognition. This study provides a framework for rational receptor engineering to enhance pathogen restriction.

摘要

表面定位的受体激酶FLS2可检测细菌鞭毛中的flg22表位。FLS2在陆地植物中保守,但细菌病原体表现出多态性的flg22表位。大多数FLS2同源物具有狭窄的识别范围,但已鉴定出四种具有扩展识别范围的同源物。通过多样性分析、AlphaFold建模和氨基酸特性,将实现扩展识别的关键残基定位到FLS2的凹面,与共受体和多态性flg22残基相互作用。合成生物学能够将来自栓皮栎(Quercus variabilis)的QvFLS2的扩展识别工程改造为具有典型识别能力的同源物。类似的方法能够将来自河岸葡萄(Vitis riparia)的FLS2对农杆菌的识别能力转移到VrFLS2中。对三个植物目进行的进化分析表明,正选择下的残基与结合共受体和flg22 C末端的残基对齐,这表明存在更多具有扩展识别能力的等位基因。我们的实验数据能够鉴定促进预测FLS2-flg22识别的特定受体氨基酸特性和AlphaFold3指标。本研究为合理的受体工程以增强病原体限制提供了框架。

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本文引用的文献

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Nat Plants. 2025 Jul 28. doi: 10.1038/s41477-025-02050-5.
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N-glycosylation facilitates the activation of a plant cell-surface receptor.N-糖基化有助于植物细胞表面受体的激活。
Nat Plants. 2024 Dec;10(12):2014-2026. doi: 10.1038/s41477-024-01841-6. Epub 2024 Nov 7.
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JCVI: A versatile toolkit for comparative genomics analysis.
番茄根系对细菌衍生肽表现出独特的、特定发育阶段的反应。
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Imeta. 2024 Jun 12;3(4):e211. doi: 10.1002/imt2.211. eCollection 2024 Aug.
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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.
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Natural variation of immune epitopes reveals intrabacterial antagonism.天然免疫表位的变异揭示了细菌内拮抗作用。
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Nature. 2024 Jun;630(8016):493-500. doi: 10.1038/s41586-024-07487-w. Epub 2024 May 8.
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