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之字形、曲折形与酶:利用结构生物学设计抗病能力

Zig, Zag, and 'Zyme: leveraging structural biology to engineer disease resistance.

作者信息

McClelland Alexander J, Ma Wenbo

机构信息

The Sainsbury Laboratory, Norwich Research Park, Norwich, NR4 7UH UK.

出版信息

aBIOTECH. 2024 Apr 11;5(3):403-407. doi: 10.1007/s42994-024-00152-w. eCollection 2024 Sep.

DOI:10.1007/s42994-024-00152-w
PMID:39279864
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11399530/
Abstract

Dynamic host-pathogen interactions determine whether disease will occur. Pathogen effector proteins are central players in such disease development. On one hand, they improve susceptibility by manipulating host targets; on the other hand, they can trigger immunity after recognition by host immune receptors. A major research direction in the study of molecular plant pathology is to understand effector-host interactions, which has informed the development and breeding of crops with enhanced disease resistance. Recent breakthroughs on experiment- and artificial intelligence-based structure analyses significantly accelerate the development of this research area. Importantly, the detailed molecular insight of effector-host interactions enables precise engineering to mitigate disease. Here, we highlight a recent study by Xiao et al., who describe the structure of an effector-receptor complex that consists of a fungal effector, with polygalacturonase (PG) activity, and a plant-derived polygalacturonase-inhibiting protein (PGIP). PGs weaken the plant cell wall and produce immune-suppressive oligogalacturonides (OGs) as a virulence mechanism; however, PGIPs directly bind to PGs and alter their enzymatic activity. When in a complex with PGIPs, PGs produce OG polymers with longer chains that can trigger immunity. Xiao et al. demonstrate that a PGIP creates a new active site tunnel, together with a PG, which favors the production of long-chain OGs. In this way, the PGIP essentially acts as both a PG receptor and enzymatic manipulator, converting virulence to defense activation. Taking a step forward, the authors used the PG-PGIP complex structure as a guide to generate PGIP variants with enhanced long-chain OG production, likely enabling further improved disease resistance. This study discovered a novel mechanism by which a plant receptor plays a dual role to activate immunity. It also demonstrates how fundamental knowledge, obtained through structural analyses, can be employed to guide the design of proteins with desired functions in agriculture.

摘要

动态的宿主 - 病原体相互作用决定疾病是否会发生。病原体效应蛋白是这种疾病发展过程中的核心因素。一方面,它们通过操纵宿主靶点来提高宿主易感性;另一方面,它们在被宿主免疫受体识别后可触发免疫反应。分子植物病理学研究的一个主要方向是了解效应蛋白与宿主的相互作用,这为抗病性增强作物的培育和育种提供了依据。基于实验和人工智能的结构分析方面的最新突破显著加速了这一研究领域的发展。重要的是,对效应蛋白 - 宿主相互作用的详细分子洞察能够实现精准工程以减轻病害。在此,我们重点介绍肖等人最近的一项研究,他们描述了一种效应蛋白 - 受体复合物的结构,该复合物由具有多聚半乳糖醛酸酶(PG)活性的真菌效应蛋白和植物源多聚半乳糖醛酸酶抑制蛋白(PGIP)组成。PG会削弱植物细胞壁并产生免疫抑制性寡聚半乳糖醛酸(OG)作为一种致病机制;然而,PGIP会直接与PG结合并改变其酶活性。当与PGIP形成复合物时,PG会产生具有更长链的OG聚合物,从而能够触发免疫反应。肖等人证明,PGIP与PG一起形成了一个新的活性位点通道,有利于长链OG的产生。通过这种方式,PGIP实际上既充当PG受体又充当酶操纵者,将致病性转化为防御激活。更进一步,作者以PG - PGIP复合物结构为指导,生成了具有增强的长链OG产生能力的PGIP变体,这可能会进一步提高抗病性。这项研究发现了一种植物受体发挥双重作用来激活免疫的新机制。它还展示了如何利用通过结构分析获得的基础知识来指导农业中具有所需功能的蛋白质的设计。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c371/11399530/2d1e26e2f4f6/42994_2024_152_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c371/11399530/2d1e26e2f4f6/42994_2024_152_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c371/11399530/2d1e26e2f4f6/42994_2024_152_Fig1_HTML.jpg

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本文引用的文献

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