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Structure-Function Analyses of Plant NLR receptors

植物 NLR 受体的结构功能分析

基本信息

批准号：
1758400
负责人：
Jeffery Dangl
金额：
$ 120万
依托单位：
University of North Carolina at Chapel Hill
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-01 至 2024-07-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1758400&HistoricalAwards=false
关键词：
Structure Function Analyses Plant NLR

项目摘要

Plants are fertile sources of nutrients for a variety of microbes. Many of these reduce plant fitness and productivity, and hence are pathogens. Plant pathogens devastate crops, particularly in developing areas where expensive (and often unsustainable) fungicides and pesticides are beyond the economic reach of most farmers. Yield losses due to plant disease are also "water losses", since that resource is often invested before disease decimates a crop. Hence, successfully combating plant diseases through rational deployment of the plant immune system will contribute directly to human and environmental health, and save lots of water. Plants possess a sophisticated immune system anchored in the functions of a family of protein, called NLR receptors, that detect the presence of pathogens and trigger a cascade of events in and around the infected cell that stops pathogen growth. Plant breeding has benefited from the ongoing definition of plant NLR function. A mechanistic understanding of NLR function is a prerequisite for rational deployment of the plant immune system in crops and for the development of treatments for various human diseases. Researchers investigating NLR experimental systems in either plants or animals recognize that it is now vital to understand how signal competent receptors are organized before infection, the precise mechanisms by which they are activated, and how this activation is translated in an appropriate output response. Hence, the broadest impacts of the proposed research project will significantly inform translation to crop species and to human health.This project focuses on the intracellular receptors of the NLR protein superfamily which are critical for pathogen detection in the innate immune systems of both plants and animals. Originally discovered in plants in the mid-1990s, NLRs are a major basis for disease resistance in plants and have been manipulated, unknowingly at first, by crop breeders as "disease resistance genes" for over a century. NLRs were subsequently discovered in animals, where they play a major role in regulating innate immune signaling in infectious and autoimmune disease. Once activated, NLRs direct a complex output response that ultimately restricts pathogen growth. Despite the central role of NLRs in innate immunity in plants and animals, there is to date no generalizable model describing how NLRs transition from an inactive resting state to an active signaling state after recognition of microbial signals. Filling this gap is the critical unresolved research issue pertaining to NLR biology in both plant and animal innate immune research, and is the focus of this project. This project is aimed at understanding particular mechanistic exemplars that span the wide gamut of NLR modularity in order to illuminate the core principles underlying NLR activation, specifically: (1) as a naturally occurring effector-activated minimal TIR only domain (RBA1); and (2) as a small family of "helper" NLRs called ADR1 proteins that use a canonical mechanism to control cell death but a non-canonical mechanism to enhance sensor NLR function and contribute to the control of salicylic acid levels.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

植物是多种微生物丰富的营养来源。其中许多降低了植物的适应性和生产力，因此是病原体。植物病原体破坏作物，特别是在发展中地区，在这些地区，大多数农民都负担不起昂贵的（而且往往是不可持续的）杀菌剂和杀虫剂。植物病害造成的产量损失也是“水损失”，因为这种资源往往是在病害摧毁作物之前投入的。因此，通过合理部署植物免疫系统，成功地对抗植物病害，将直接有助于人类和环境的健康，并节省大量的水。植物拥有一个复杂的免疫系统，它依赖于一种被称为NLR受体的蛋白质家族的功能，这种蛋白质家族可以检测病原体的存在，并在受感染细胞内部和周围触发一系列事件，阻止病原体的生长。植物育种得益于对植物NLR功能的不断界定。对NLR功能的机制理解是作物中合理部署植物免疫系统和开发各种人类疾病治疗方法的先决条件。研究植物或动物NLR实验系统的研究人员认识到，现在至关重要的是要了解信号受体在感染前是如何组织的，它们被激活的确切机制，以及这种激活如何转化为适当的输出反应。因此，拟议研究项目的最广泛影响将为作物物种和人类健康的转化提供重要信息。本项目主要研究NLR蛋白超家族的细胞内受体，这些受体在植物和动物的先天免疫系统中对病原体检测至关重要。nlr最初是在20世纪90年代中期在植物中发现的，是植物抗病的主要基础，并在一个多世纪以来被作物育种者作为“抗病基因”操纵，起初是在不知情的情况下。nlr随后在动物中被发现，它们在调节感染性和自身免疫性疾病的先天免疫信号中起主要作用。NLRs一旦被激活，就会引导复杂的输出反应，最终限制病原体的生长。尽管NLRs在植物和动物的先天免疫中起着核心作用，但迄今为止还没有一个可推广的模型来描述NLRs在识别微生物信号后如何从无活性的静息状态转变为活跃的信号状态。填补这一空白是植物和动物先天免疫研究中NLR生物学尚未解决的关键研究问题，也是本项目的重点。该项目旨在理解跨越NLR模块化大范围的特定机制范例，以阐明NLR激活的核心原则，具体而言：(1)作为自然发生的效应激活的最小TIR域（RBA1）；(2)作为一个小的“辅助”NLR家族，称为ADR1蛋白，它使用规范机制来控制细胞死亡，但非规范机制来增强传感器NLR功能并有助于控制水杨酸水平。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。