提出问题：Global NLR homeostasis must be tightly controlled to ensure sufficient and timely immune output while avoiding aberrant activation, the mechanisms of which are largely unclear.

结果：In a previous reverse genetic screen, we identified two novel E3 ligases, SNIPER 1 and its homolog SNIPER 2, both of which broadly control the levels of NLR immune receptors in Arabidopsis. Protein levels of sensor NLRs (sNLRs) are inversely correlated with SNIPER 1 amount and the interactions between SNIPER 1 and sNLRs seem to be through the common nucleotide‐binding (NB) domains of sNLRs. In support, SNIPER 1 can ubiquitinate the NB domains of multiple sNLRs in vitro.

结论：Our study thus reveals a novel process of global turnover of sNLR s by two master E3 ligases for immediate attenuation of immune output to effectively avoid autoimmunity.

展望：Such unique mechanism can be utilized in the future for engineering broad‐spectrum resistance in crops to fend off pathogens that damage our food supply.

 摘  要 

在动植物中，核苷酸结合亮氨酸富含重复NLR免疫受体感知来自于病原菌的分子，以此来诱导免疫响应。生物必须严格控制自身的NLR内稳态，从而保证有效并及时的免疫输出，避免异常激活，但是其具体的分子机制还不清楚。在先前的反向遗传学筛选过程中，作者鉴定到了两个新的E3连接酶SNIPER 1和SNIPER 2，这两个蛋白都能够广泛控制拟南芥中NLR免疫受体的水平。感应NLRs（sensor NLRs）的蛋白水平与SNIPER 1蛋白的量呈现负相关，而且SNIPER 1与感应NLRs之间的互作似乎是通过感应NLRs的一个共有的核苷酸结合结构域来进行的。在体外条件下，SNIPER 1可以泛素化多个感应NLRs的核苷酸结合结构域。本文的研究揭示了一个新的植物感应NLRs整体周转的机制，其中两个E3连接酶发挥主要作用，从而减弱免疫输出，有效避免自身免疫。该机制可用于未来人工构建作物的广谱抗性，帮助作物抵御破坏食物供给的病原菌。

 通讯作者