Liu Furong, Yang Zhenlin, Wang Chao, Martin Raoul, Qiao Wenjie, Carette Jan E, Luan Sheng, Nogales Eva, Staskawicz Brian
bioRxiv. 2024 Jan 9:2023.12.18.571367. doi: 10.1101/2023.12.18.571367.
Innate immune responses against microbial pathogens in both plants and animals are regulated by intracellular receptors known as Nucleotide-binding Leucine-rich Repeats (NLR) proteins. In plants, these NLRs play a crucial role in recognizing pathogen effectors, thereby initiating the activation of immune defense mechanisms. Notably, certain NLRs serve as "helper" NLR immune receptors (hNLR), working in tandem with "sensor" NLR immune receptors (sNLR) counterparts to orchestrate downstream signaling events to express disease resistance. In this study, we reconstituted and determined the cryo-EM structure of the hNLR required for cell death 4 (NRC4) resistosome. The auto-active NRC4 formed a previously unanticipated hexameric configuration, triggering immune responses associated with Ca influx into the cytosol. Furthermore, we uncovered a dodecameric state of NRC4, where the coil-coil (CC) domain is embedded within the complex, suggesting an inactive state, and expanding our understanding of the regulation of plant immune responses.
The hexameric NRC4 resistosome mediates cell death associated with cytosolic Ca influx.
植物和动物针对微生物病原体的天然免疫反应由称为核苷酸结合富含亮氨酸重复序列（NLR）蛋白的细胞内受体调节。在植物中，这些NLR在识别病原体效应子方面发挥关键作用，从而启动免疫防御机制的激活。值得注意的是，某些NLR作为“辅助”NLR免疫受体（hNLR），与“传感器”NLR免疫受体（sNLR）协同工作，协调下游信号事件以表达抗病性。在本研究中，我们重构并确定了细胞死亡4（NRC4）抗病小体所需的hNLR的冷冻电镜结构。自身激活的NRC4形成了一种先前未预料到的六聚体构型，触发了与Ca流入细胞质相关的免疫反应。此外，我们发现了NRC4的十二聚体状态，其中卷曲螺旋（CC）结构域嵌入复合物中，表明是一种无活性状态，并扩展了我们对植物免疫反应调节的理解。
六聚体NRC4抗病小体介导与细胞质Ca流入相关的细胞死亡。
