Molecular Basis of NLR-Mediated Innate Immunity in Arabidopsis thaliana

拟南芥 NLR 介导的先天免疫的分子基础

基本信息

批准号：
8204764
负责人：
BRIAN John STASKAWICZ
金额：
$ 33.93万
依托单位：
UNIVERSITY OF CALIFORNIA BERKELEY
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-09-29 至 2014-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8204764
关键词：
3-Dimensional Amino Acids Animals Arabidopsis Arabidopsis Proteins Arabidopsis RIN4 protein Biochemical Biochemical Genetics Biological Assay Cell Wall Cell membrane Chloroplasts Collection Cyclophilins Cytoplasm Data Development Dimerization Disease Resistance Event Excision Gene Targeting Genes Goals Hybrids Immune System Diseases Immune response Immunity Immunologic Receptors Infection Integrins Laboratories Lead Libraries Location Luciferases Mammals Mediating Modeling Molecular Molecular Models Mouse-ear Cress Mutate Mutation N-terminal NDRG1 gene Natural Immunity Pathway interactions Perception Plants Play Protein Family Proteins Proteomics Pseudomonas syringae RNA Regulation Research Resistance Role Signal Pathway Signal Transduction Signal Transduction Pathway Stream Structure Sucrose Technology Testing Work Yeasts base biological adaptation to stress design dimer functional genomics innovation insight molecular modeling mutant next generation novel pathogen prevent promoter protein activation protein folding protein function public health relevance receptor research study response transcription factor

项目摘要

DESCRIPTION (provided by applicant): The long-term objectives of this project are to elucidate the molecular basis of plant innate immunity in response to bacterial pathogens. In this application, experiments will be carried out to elucidate the molecular basis of bacterial pathogen recognition by the NLR class of innate immune receptors in Arabidopsis thaliana. A major aim of these studies is the identification and characterization of the downstream signaling events that result from the activation of NLR proteins. The NLR protein family of immune receptors was originally described in plants as the major class of disease resistance (R) proteins that control disease resistance in plants. Subsequently, it was discovered that this class of protein also functions in animals as innate immune receptors as more than twenty have been described to date. Our research will focus on the role of the NDR1 and RIN4 proteins in both PAMP and effector-triggered immunity. Our recent results have revealed that NDR1 protein compromises both flg22-induced innate immunity and the RPS2 signal transduction pathway. Interestingly, the NDR1 shares protein folds and a predicted 3-D structure with the LEA14 protein that has been shown to be involved in abiotic stress responses. The predicted 3-D structure of NDR1 will allow us to perform a structure and function analysis by mutating amino acids that are predicted to be involved function and will allow us to ascertain the role NDR1 plays in immune receptor location and signal transduction. Furthermore, we propose to study the molecular events associated with the negative regulation of the RPS2 protein by the Arabidopsis RIN4 protein and the subsequent activation the AvrRpt2 effector protein. Once the RPS2 protein is activated, this application will identify and characterize the direct targets of the activated RPS2 protein by employing next-generation Illumina sequencing technologies in conjunction with a comprehensive yeast-one hybrid library that represents all the transcription factors known to date in Arabidopsis. To accomplish these goals, experimental approaches will be designed to employ a combination of biochemical, genetic, cellular, proteomic and functional genomic approaches to characterize the signal transduction events controlling the expression of disease resistance in this model pathosystem. PUBLIC HEALTH RELEVANCE: Our research goal is to provide a molecular understanding of the biochemical events that are involved in activating NLR immune receptor proteins in plants. Understanding the molecular basis of NLR protein activation by pathogen signals will provide novel insights and provide an mechanistic explanation as to how these proteins function and ultimately will lead to the development of innovative strategies for the control of infectious and auto-immune disease in both animals and plants.

描述（由申请人提供）：该项目的长期目标是阐明植物针对细菌病原体的先天免疫的分子基础。在本申请中，将进行实验来阐明拟南芥中 NLR 类先天免疫受体识别细菌病原体的分子基础。这些研究的主要目的是鉴定和表征 NLR 蛋白激活引起的下游信号事件。免疫受体的 NLR 蛋白家族最初在植物中被描述为控制植物抗病性的主要一类抗病 (R) 蛋白。随后，人们发现这类蛋白质在动物中也起到先天免疫受体的作用，迄今为止已描述了二十多种蛋白质。我们的研究将重点关注 NDR1 和 RIN4 蛋白在 PAMP 和效应子触发免疫中的作用。我们最近的结果表明，NDR1 蛋白会损害 flg22 诱导的先天免疫和 RPS2 信号转导途径。有趣的是，NDR1 与 LEA14 蛋白共享蛋白折叠和预测的 3-D 结构，LEA14 蛋白已被证明参与非生物胁迫反应。 NDR1 的预测 3-D 结构将使我们能够通过突变预测涉及功能的氨基酸来进行结构和功能分析，并使我们能够确定 NDR1 在免疫受体定位和信号转导中发挥的作用。此外，我们建议研究与拟南芥 RIN4 蛋白对 RPS2 蛋白负调节相关的分子事件以及随后激活 AvrRpt2 效应蛋白。一旦 RPS2 蛋白被激活，该应用程序将通过采用下一代 Illumina 测序技术以及代表拟南芥中迄今为止已知的所有转录因子的综合酵母一杂合文库来识别和表征激活的 RPS2 蛋白的直接靶标。为了实现这些目标，实验方法将被设计为采用生化、遗传、细胞、蛋白质组和功能基因组方法的组合来表征控制该模型病理系统中抗病性表达的信号转导事件。公共健康相关性：我们的研究目标是提供对植物中参与激活 NLR 免疫受体蛋白的生化事件的分子理解。了解病原体信号激活 NLR 蛋白的分子基础将为这些蛋白如何发挥作用提供新的见解和机制解释，并最终导致开发控制动物和人类感染和自身免疫性疾病的创新策略。植物。