Mechanistic Insights into the Plant Disease Resistance Mediated by NPR1

项目摘要/摘要 NPR1(PATHOGENSIS相关基因的NONEXPRESSOR of PATHOGENSIS相关基因1)是植物体内的主要免疫调节因子。它 通过激活病程相关(PR)基因来协调系统获得性抵抗(SAR) 在植物对病原挑战的反应中，对水杨酸(SA)诱导的反应。广泛的遗传 生化研究表明，NPR1是SA的受体。NPR1的SA激活触发基因组- 通过NPR1与多种转录激活物和抑制物的相互作用进行广泛的转录重编程。 NPR1本身受氧化还原剂的调节，其蛋白水解性转换在广泛的范围内具有深远的意义 生物学功能，包括昼夜节律和内质网对蛋白毒性应激的抵抗力 网状结构。尽管NPR1在植物生物学中扮演着重要的角色，但无数 NPR1的功能在很大程度上仍不清楚。在我们初步成功地阐明了 Apo NPR1使用单粒子低温EM，在这里我们建议阐明NPR1功能的分子基础 在植物中。具体来说，我们将解决(1)SA如何激活NPR1，(2)NPR1如何与转录相互作用 因素和调节器，以及(3)NPR1是如何降解的。从这些研究中获得的信息将提供 对SA-NPR1信号级联的迫切需要的机械性见解有助于植物发展疾病- 抗病作物。由于SA是阿司匹林的主要代谢物，这样的知识也可能有助于更好地 了解SA及其类似物对人类的医学益处。

Project Summary/Abstract NPR1 (NONEXPRESSOR OF PATHOGENSIS-RELATED GENES 1) is a master immune regulator in plants. It orchestrates systemic acquired resistance (SAR) by activating PATHOGENESIS-RELATED (PR) genes in response to induction of salicylic acid (SA) during the plant response to pathogenic challenges. Extensive genetic and biochemical studies have shown that NPR1 is a receptor of SA. SA activation of NPR1 triggers genome- wide transcriptional reprograming via NPR1 interactions with a variety of transcription activators and repressors. NPR1 itself is regulated by redox agents, and its proteolytic turnover has profound implications in a wide range of biological functions, including circadian rhythm and resistance to proteotoxic stress in the endoplasmic reticulum. Despite the essential role of NPR1 in plant biology, the molecular details underlying the myriad of NPR1 functions have remained largely unknown. Building upon our initial success in elucidating the structure of apo NPR1 using single-particle cryoEM, here we propose to elucidate the molecular basis of the NPR1 function in plants. Specifically, we will address (1) how SA activates NPR1, (2) how NPR1 interacts with transcription factors and regulators, and (3) how NPR1 is degraded. Information gained from these studies will provide the much-needed mechanistic insights into the SA-NPR1 signaling cascade in plants and help develop disease- resistant crops. As SA is the principle metabolite of aspirin, such knowledge may also contribute to a better understanding of the well-documented medicinal benefits of SA and analogs in humans.