In the field of plant immunity, the arms race between host and pathogen is often vividly described as a "zig-zag" similar step-by-step tug-of-war: plants respond to the invasion of most pathogens through the basic innate immune system, while adaptive pathogens overcome the host's defense mechanisms by secreting a series of effector proteins to promote their infection; Deciphering the specific interaction mechanism between pathogen effector proteins and plant receptors is a major research direction in plant molecular pathology, which can provide a solid and reliable theoretical basis for crop breeding and development to enhance disease resistance. Recently, Professor Jijie Chai from Westlake University/Tsinghua University and Professor Yuanchao Wang from Nanjing Agricultural University published "A plant mechanism of hijacking pathogen virulence factors to trigger innate immunity" in Science This research is of great significance for the development of resistant crop breeding based on the plant receptor PGIP hijacking pathogen cell wall degrading enzyme effector protein PG, and has received extensive attention from experts and scholars in the field of plant immunity.
近日，aBIOTECH特邀英国塞恩斯伯里实验室（The Sainsbury Laboratory）马文勃教授针对此项重要成果，发表了题为“Zig, Zag, and ’Zyme: leveraging structural biology to engineer disease resistance”的评述文章（点击题目阅读全文）。
Wenbo Ma, Alexander J. McClelland
In this article, Prof. Ma Wenbo's team first systematically introduced PGIP-PG, a plant classical immune signaling pathway. The source of the pathogen polygalacturonase (PG) is a class of degrading enzymes that hydrolyze demethylated pectin (polygalacturonic acid, PGA) from the cell wall to short-chain polygalacturonic acid (OG). The toxicity of PG can be further enhanced due to the function of inhibiting plant immunity. Plants usually secrete a variety of extracellular inhibitory proteins, which specifically bind to the enzyme pockets of pathogen cell wall degrading enzymes, inhibit substrates from binding to them, and destroy their cell wall degradation activity.
The pathogen PG can be recognized by the plant extracellular secretory LRR receptor PGIP, and the extracellular secretion protein that binds to PG is named PG-inhibiting protein (PGIP). Unlike common LRR receptor kinase/receptor proteins, which are localized on the cell membrane, PGIP lacks a permeable and intracellular region, suggesting that it primarily plays a role outside the cell. However, unlike common "inhibitory proteins", biochemical experiments have shown that PGIP can significantly change the product of PG hydrolysis of PGA to generate long-chain OG (OG10-15) with a degree of polymerization of 10-15. These OG10-15 act as signals that can be recognized by the receptor kinase WAK, activating the plant immune response. This peculiar phenomenon has been discovered for more than 30 years, but the molecular mechanism by which PGIP changes the activity of PG enzyme is still unknown.
Subsequently, the review systematically reviewed the results of the research in the Science paper (Figure 1). Dr. Yu Xiao, the first author of the paper, and his collaborators reconstituted the complex formed by PvPGIP2 from Phaseolus vulgaris and Fusarium FpPG in vitro, and enzymatic and in vivo experiments proved that different hydrolysates of PvPGIP2-FpPG-PGA and FpPG-PGA can exert immune activation and immunosuppressive functions, respectively. The structure of the PvPGIP2-FpPG complex showed that PvPGIP2 did not bind to the enzyme activity center of FpPG, and PvPGIP2 combined with FpPG to form a new and longer substrate OG binding pocket, and PvPGIP2 enhanced the binding ability of substrate OG to FpPG. PvPGIP2-FpPG is a novel polygalacturonic acid hydrolase composed of cross-species proteins, which has different substrate selectivity and catalytic activity from FpPG. Based on the analytic structure of the high-resolution PvPGIP2-FpPG complex, the researchers carried out two types of engineering modifications on PGIP: first, the modified PvPGIP2 has the ability to produce more OG10-15, and second, the modified alfalfa MtPGIP1 can obtain the FpPG recognition ability that it does not have.
Fig.1 PvPGIP2 induces plant immune response by altering FpPG enzyme activity
Because PGIP and PG are widely present in the plant kingdom and pathogens, PGIP has been shown to play an important role in the process of disease resistance in many plants. The successful directional transformation of PGIP in this paper reveals that it may have great application potential in the development and breeding of resistant crops in the future. In addition, this review also looks forward to the feasible research directions in the PGIP-PG-related signaling pathway in the future. For example, the sequence and structural changes of PGIP and PG in nature are studied in depth, the mechanism of PG escape PGIP manipulation is analyzed, and the ability of PGIP to effectively monitor PG of various pathogens in high-quality crop varieties is enhanced.
Finally, this paper cites a series of successful protein targeted modifications in the field of plant disease resistance based on the analysis of high-resolution complex structures, artificial intelligence protein design, and Alphafold multimer structure prediction by many plant immunologists in recent years. There is no doubt that with the further understanding of the molecular mechanisms of plant-pathogen interactions, the era of structure-oriented engineering of disease-resistant proteins has arrived, and it is reasonable to expect that they will shine in the future in applications that enhance crop resistance and improve crop yields.
Quote text:
McClelland, A.J., Ma, W. Zig, Zag, and ’Zyme: leveraging structural biology to engineer disease resistance. aBIOTECH (2024). https://doi.org/10.1007/s42994-024-00152-w
肖裕，清华大学水木学者、北京生物结构前沿中心卓越学者、清华大学生命科学学院博士后。 博士与博士后阶段均师从西湖大学（原清华大学）世界知名植物免疫学家柴继杰教授。 主要研究方向为植物先天免疫受体的结构与功能研究，博士阶段聚焦于植物CrRLK1L受体激酶，揭示了该家族中明星受体FER与膜锚定蛋白LLG共同识别肽类激素RALF的分子机制（Xiao et al, Nature, 2019）；博士后阶段工作主要聚焦于植物分泌LRR受体，揭示了植物PGIP识别病原体PG，劫持其酶活来激活植物免疫的分子机制（Xiao et al, Science, 2024）。 目前已累计发表论文12篇，总引用量>600次（Google Scholar）。 其中以第一作者（含共同）在Nature, Science, Molecular Cell, Nature Communications, Nucleic Acid Research上发表文章5篇。
Dr. Xiao Yu is currently planning to establish an independent laboratory in the new institution, and future research will focus on structural biology, focusing on plant receptor kinases and plant cell wall-related signaling pathways. Graduate students and postdoctoral fellows who are interested in their field of work and are interested in exploring the mysteries of plant life together are welcome to contact [email protected] through the following email.
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