The Sw-5b NLR nucleotide-binding domain plays a role in oligomerization, and its self-association is important for activation of cell death signaling
The Sw-5b NLR nucleotide-binding domain plays a role in oligomerization, and its self-association is important for activation of cell death signaling
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Sw-5b NLR 核苷酸结合结构域在寡聚化中发挥作用，其自缔合对于激活细胞死亡信号传导非常重要
DOI：
10.1093/jxb/erab279
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发表时间：
2021
影响因子：
6.9
通讯作者：
Tao Xiaorong
中科院分区：
文献类型：
--
作者：
Zhao Xiaohui;Chen Zhengqiang;Wu Qian;Cai Yazhen;Zhang Yu;Zhao Ruizhen;Yan Jiaoling;Qian Xin;Li Jia;Zhu Min;Hong Lizhou;Xing Jincheng;Khan Nasr Ullah;Ji Yinghua;Wu Peijun;Huang Changjun;Ding Xin Shun;Zhang Hui;Tao Xiaorong
植物和动物细胞内的核苷酸结合和富含亮氨酸重复序列（NLR）受体在感知病原体和激活防御信号中起着重要作用。然而，NLR蛋白激活宿主防御信号的分子机制在很大程度上仍然未知。许多研究已经确定NLR蛋白的卷曲-卷曲（CC）或Toll和白介素-1受体/抗性蛋白（TIR）结构域及其二聚/寡聚化对于激活下游防御信号传导至关重要。在这项研究中，我们证明，在番茄中，核苷酸结合（NB）结构域Sw-5 b NLR单独可以激活下游防御信号，导致激发子非依赖性细胞死亡。Sw-5 b NB结构域可以自缔合，这种自缔合对于激活细胞死亡信号传导至关重要。在NB结构域的P环中引入K568 R突变后，自缔合受到强烈损害。因此，NBK 568 R突变体诱导的细胞死亡非常弱。缺失C-末端20个氨基酸的NBCΔ 20突变体可以自缔合，但不能激活细胞死亡信号。NBCΔ 20突变体还干扰野生型NB结构域的自结合，导致细胞死亡诱导受损。相比之下，NBK 568 R突变体不干扰野生型NB结构域的自缔合及其诱导细胞死亡的能力。Sw-5 b的结构建模表明NB结构域彼此关联并且可能参与寡聚化。由于Sw-5 b触发的细胞死亡依赖于辅助NLR蛋白，我们提出Sw-5 b NB结构域可能通过招募下游辅助伙伴来触发防御信号，从而作为寡聚抗性体组装的成核点。
Plant and animal intracellular nucleotide-binding and leucine-rich repeat (NLR) receptors play important roles in sensing pathogens and activating defense signaling. However, the molecular mechanisms underlying the activation of host defense signaling by NLR proteins remain largely unknown. Many studies have determined that the coil–coil (CC) or Toll and interleukin-1 receptor/resistance protein (TIR) domain of NLR proteins and their dimerization/oligomerization are critical for activating downstream defense signaling. In this study, we demonstrated that, in tomato, the nucleotide-binding (NB) domain Sw-5b NLR alone can activate downstream defense signaling, leading to elicitor-independent cell death. Sw-5b NB domains can self-associate, and this self-association is crucial for activating cell death signaling. The self-association was strongly compromised after the introduction of a K568R mutation into the P-loop of the NB domain. Consequently, the NBK568Rmutant induced cell death very weakly. The NBCΔ20mutant lacking the C-terminal 20 amino acids can self-associate but cannot activate cell death signaling. The NBCΔ20mutant also interfered with wild-type NB domain self-association, leading to compromised cell death induction. By contrast, the NBK568Rmutant did not interfere with wild-type NB domain self-association and its ability to induce cell death. Structural modeling of Sw-5b suggests that NB domains associate with one another and likely participate in oligomerization. As Sw-5b-triggered cell death is dependent on helper NLR proteins, we propose that the Sw-5b NB domain acts as a nucleation point for the assembly of an oligomeric resistosome, probably by recruiting downstream helper partners, to trigger defense signaling.