论文题目：Durable rust resistance in wheat conferred by engineering host protein TaHRLI to evade recognition by the virulence effector PstCRT
论文作者：Shuangyuan Guo, Yanqin Zhang, Xinmei Zhang, Xiaoya Du, Feng Zhang, Huankun Li, Xiaojie Wang, Zhensheng Kang, Xinmei Zhang
论文摘要： Endoplasmic reticulum (ER) stress and the hypersensitive response (HR) are recognized as cornerstones of plant immunity; however, the mechanistic synergy and the strategies pathogens employ to dismantle this alliance remain elusive. Here, we identify a virulence effector PstCRT (calreticulin) from Puccinia striiformis f. sp. tritici (Pst), that suppresses host immune responses by disrupting ER stress-mediated HR. PstCRT directly targets the HR-like lesion-inducing protein (TaHRLI) in wheat and obstructs its ER translocation. Within the ER lumen, TaHRLI interacts with wheat calreticulin (TaCRT), triggering Ca²⁺ efflux and activating the unfolded protein response (UPR) to induce cell death and disease resistance. Pathogen-derived PstCRT structurally mimics TaCRT to sequester TaHRLI to the plasma membrane via competitive interaction, thereby effectively suppressing ER stress-induced HR initiation. Crucially, we found that CRT secretion represents a conserved virulence strategy across different rust genera, AlphaFold-guided engineering of TaHRLI in wheat generated the TaHRLIMut variant that evades PstCRT recognition. Overexpressing TaHRLIMut in wheat conferred broad-spectrum resistance against Pst in biennial field trials, effectively mitigating pathogen-induced yield losses while preserving essential agronomic traits. Collectively, this study elucidates a molecular mechanism underlying pathogen disruption of ER stress-induced HR to promote infection and proposes an innovative strategy for engineering durable crop protection.
内质网（ER）应激和超敏反应（HR）被认为是植物免疫的基石；然而，其机制上的协同作用以及病原体为瓦解这一联盟所采用的策略仍不为人所知。在此，我们鉴定出来自锈菌（Puccinia striiformis f. sp. tritici）的毒力因子 PstCRT（钙网蛋白），它通过破坏内质网应激介导的超敏反应来抑制宿主免疫反应。PstCRT 直接靶向小麦超敏反应诱导蛋白（TaHRLI），并阻止其在内质网中的转运。在内质网腔内，TaHRLI 与小麦钙网蛋白（TaCRT）相互作用，引发钙离子外流，并激活未折叠蛋白反应（UPR）以诱导细胞死亡和抗病性。病原体衍生的 PstCRT 结构上模仿 TaCRT，通过竞争性相互作用将 TaHRLI劫持至细胞膜，从而有效地抑制由内质网应激引发的超敏反应。至关重要的是，我们发现CRT分泌是不同锈菌属之间的一种保守毒力策略。通过 AlphaFold指导对小麦 TaHRLI 进行改造，产生了逃避 PstCRT 识别的 TaHRLIMut 变体。在小麦中过表达TaHRLIMut赋予了其对 条锈菌广谱抗性，有效地减少了病原体导致的产量损失，同时保留了重要农艺性状。综上，这项研究阐明了病原体破坏内质网应激诱导的免疫反应以促进感染的分子机制，并提出了一个创新的策略来实现作物的持久保护。
论文链接：https://authors.elsevier.com/a/1mYLa3QW8SDrYB