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

• 批准号: 8041669
• 负责人: BRIAN John STASKAWICZ
• 金额: $ 33.99万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 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/8041669
• 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; receptor; research study; response; transcription factor

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对细菌病原体的植物先天免疫的分子基础。在此应用中，将进行实验，以阐明NLR先天免疫受体在拟南芥中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蛋白激活导致的下游信号事件。免疫受体的NLR蛋白家族最初在植物中描述为控制植物中抗病性的主要抗病性（R）蛋白。随后，发现这类蛋白质在动物中也起着先天免疫受体的作用，因为迄今已描述了二十多种。我们的研究将集中于NDR1和RIN4蛋白在PAMP和效应触发的免疫力中的作用。我们最近的结果表明，NDR1蛋白损害了FLG22诱导的先天免疫力和RPS2信号转导途径。有趣的是，NDR1与Lea14蛋白共享蛋白质褶皱和预测的3-D结构，该蛋白已被证明与非生物应力反应有关。 NDR1的预测3-D结构将使我们能够通过突变被预测涉及功能的氨基酸进行结构和功能分析，并使我们能够确定NDR1在免疫受体位置和信号转导中的作用。此外，我们建议研究拟南芥RIN4蛋白与RPS2蛋白负调控的分子事件以及随后的激活AVRRPPT2效应蛋白。一旦激活了RPS2蛋白，该应用将通过使用下一代Illumina测序技术以及代表拟南芥已知的所有转录因子的全面酵母单杂交库结合使用下一代Illumina测序技术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，将设计实验方法，以采用生化，遗传，细胞，蛋白质组学和功能基因组方法的结合，以表征控制该模型病态疾病抗性表达的信号转导事件。 公共卫生相关性：我们的研究目标是对激活植物中NLR免疫受体蛋白的生化事件提供分子理解。了解病原体信号激活NLR蛋白的分子基础将提供新颖的见解，并为这些蛋白质发挥作用以及最终如何导致控制动物和植物中感染和自身免疫性疾病的创新策略提供一种机械解释。